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The risk of childhood leukaemia following exposure to ionising radiation - A review
Abstract
Since the early years of follow-up of the Japanese atomic-bomb survivors, it has been apparent that childhood leukaemia has a particular sensitivity to induction by ionising radiation, the excess relative risk (ERR) being expressed as a temporal wave with time since exposure. This pattern has been generally confirmed by studies of children treated with radiotherapy. Case-control studies of childhood leukaemia and antenatal exposure to diagnostic x-rays, a recent large cohort study of leukaemia following CT examinations of young people, and a recent large case-control study of natural background γ-radiation and childhood leukaemia have found evidence of raised risks following low-level exposure. These findings indicate that an ERR/Sv for childhood leukaemia of ∼50, which may be derived from risk models based upon the Japanese atomic-bomb survivors, is broadly applicable to low dose or low dose-rate exposure circumstances.
... Since cosmic ray intensity increases with altitude, cabin crew members statistically face a larger risk of having cancer relative to the general population (37), and there also is a similar danger for the people spending a lot of time in the mountains. It has been found that there is a direct relationship between the frequency of childhood leukemia incidence and exposure to ultraviolet radiation (38), diagnostic X-rays and natural background ionizing radiation (39). The relationship between the solar activity reflected in the so-called Wolf numbers of sunspots and the incidence of leukemia in cohorts of young children aged 0-14 years has been claimed in several studies (26,40). ...
... The relationship between the solar activity reflected in the so-called Wolf numbers of sunspots and the incidence of leukemia in cohorts of young children aged 0-14 years has been claimed in several studies (26,40). There is evidence for a link between all potentially adverse factors mentioned above and cancer, including leukemia, although more studies are necessary to understand the mechanisms behind it (39). ...
Leukemia is the most common cancer in children. Its incidence has been increasing worldwide since 1910th, suggesting the presence of common sources of the disease, most likely related to people’s lifestyle and environment. Understanding the relationship between childhood leukemia and environmental conditions is critical to preventing the disease. This discussion article examines established potentially-carcinogenic environmental factors, such as vehicle emissions and fires, alongside space weather-related parameters like cosmic rays and the geomagnetic field. To discern the primary contributor, we analyze trends and annual variations in leukemia incidence among 0-14-year-olds in the United States, Canada, Australia, and Russia from 1990 to 2018. Comparisons are drawn with the number of vehicles (representing gasoline emissions) and fire-affected land areas (indicative of fire-related pollutants), with novel data for Russia introduced for the first time. While childhood leukemia incidence is rising in all countries under study, the rate of increase in Russia is twice that of other nations, possibly due to a delayed surge in the country’s vehicle fleet compared to others. This trend in Russia may offer insights into past leukemia levels in the USA, Canada, and Australia. Our findings highlight vehicular emissions as the most substantial environmental hazard for children among the factors examined. We also advocate for the consideration of potential modulation of carcinogenic effects arising from variations in cosmic ray intensity, as well as the protective role of the geomagnetic field. To support the idea, we provide examples of potential space weather effects at both local and global scales. The additional analysis includes statistical data from 49 countries and underscores the significance of the magnetic field dip in the South Atlantic Anomaly in contributing to a peak in childhood leukemia incidence in Peru, Ecuador and Chile. We emphasize the importance of collectively assessing all potentially carcinogenic factors for the successful future predictions of childhood leukemia risk in each country.
... Several epidemiological studies of populations exposed to high to moderate doses of ionizing radiation have shown an increased risk of cancer [6][7][8][9]. Increased risk of cancer with decreasing age at exposure has been described [2,10], hence fetuses and children are more radiosensitive [2]. ...
... Since former reviews of literature on children exposed to medical diagnostic radiation [9,[16][17][18][19] did not include recent ...
Background:
Ionizing radiation use for medical diagnostic purposes has substantially increased over the last three decades. Moderate to high doses of radiation are well established causes of cancer, especially for exposure at young ages. However, cancer risk from low-dose medical imaging is debated.
Objective:
To review the literature on cancer risks associated with prenatal and postnatal medical diagnostic ionizing radiation exposure among children and to assess this risk through a meta-analysis.
Materials and methods:
A literature search of five electronic databases supplemented by a hand search was performed to retrieve relevant epidemiological studies published from 2000 to 2019, including patients younger than 22 years of age exposed to medical imaging ionizing radiation. Pooled odds ratio (ORpooled) and pooled excess relative risk (ERRpooled) representing the excess of risk per unit of organ dose were estimated with a random effect model.
Results:
Twenty-four studies were included. For prenatal exposure (radiographs or CT), no significant increased risk was reported for all cancers, leukemia and brain tumors. For postnatal exposure, increased risk was observed only for CT, mostly for leukemia (ERRpooled=26.9 Gy-1; 95% confidence interval [CI]: 2.7-57.1) and brain tumors (ERRpooled=9.1 Gy-1; 95% CI: 5.2-13.1).
Conclusion:
CT exposure in childhood appears to be associated with increased risk of cancer while no significant association was observed with diagnostic radiographs.
... childhood leukaemia and central nervous system (CNS) tumours [1,2]. A number of environmental factors have been suggested that could partially explain cancer risks in the general population, including traffic-related air pollution [3], background radiation [2,4] and agricultural pesticides [5]. ...
... childhood leukaemia and central nervous system (CNS) tumours [1,2]. A number of environmental factors have been suggested that could partially explain cancer risks in the general population, including traffic-related air pollution [3], background radiation [2,4] and agricultural pesticides [5]. These risk factors vary in space and it is thus natural to expect spatial variation in childhood cancer incidence. ...
Background:
The aetiology of most childhood cancers is largely unknown. Spatially varying environmental factors such as traffic-related air pollution, background radiation and agricultural pesticides might contribute to the development of childhood cancer. This study is the first investigation of the spatial disease mapping of childhood cancers using exact geocodes of place of residence.
Methods:
We included 5947 children diagnosed with cancer in Switzerland during 1985-2015 at 0-15 years of age from the Swiss Childhood Cancer Registry. We modelled cancer risk using log-Gaussian Cox processes and indirect standardisation to adjust for age and year of diagnosis. We examined whether the spatial variation of risk can be explained by modelled ambient air concentration of NO2, modelled exposure to background ionising radiation, area-based socio-economic position (SEP), linguistic region, duration in years of general cancer registration in the canton or degree of urbanisation.
Results:
For all childhood cancers combined, the posterior median relative risk (RR), compared to the national level, varied by location from 0.83 to 1.13 (min to max). Corresponding ranges were 0.96 to 1.09 for leukaemia, 0.90 to 1.13 for lymphoma, and 0.82 to 1.23 for central nervous system (CNS) tumours. The covariates considered explained 72% of the observed spatial variation for all cancers, 81% for leukaemia, 82% for lymphoma and 64% for CNS tumours. There was weak evidence of an association of CNS tumour incidence with modelled exposure to background ionising radiation (RR per SD difference 1.17; 0.98-1.40) and with SEP (1.6; 1.00-1.13).
Conclusion:
Of the investigated diagnostic groups, childhood CNS tumours showed the largest spatial variation. The selected covariates only partially explained the observed variation of CNS tumours suggesting that other environmental factors also play a role.
... (Hindley et al.,2021). (Wakeford, 2013). It was noted that the rate of infection increased among workers in the field of radiation who had been exposed to radiation for long periods and in large doses (Yoshinaga et al., 2004)Also, chemotherapy has been associated with an increase in the incidence of leukemia, especially if it is used with radiotherapy such as melphalan, chlorambucil, which are associated with an increase in AML infections (Leone et al.,2007). ...
Acute Myeloid Leukemia (AML) was a type of blood cancer
characterized by the presence of abnormal cells that build up in the bone
marrow and blood. The word "acute" in acute myelogenous leukemia refers
to the rapid progression of the disease. It is called myelogenous leukemia
because it affects a group of myeloid stem cells (white blood cells, Red
blood cells and Platelets). AML was a life-threatening disease and a
common occurrence in the elderly.
The current study was designed to evaluate some immune markers (TLR-
9, IL-6 and, TNF-α) and their Correlation to AML disease, in addition to
studying the Single Nucleotide Polymorphism of the TLR-9 gene located in
the region of the promoter and the second exon. This is due to the effective
role of this gene in increasing the risk of cancer and possibly predicting the
occurrence of the disease.
A total of 120 samples were collected, 60 of them were AML patients
and 60 as apparently healthy people from Baghdad Hospital and Al-Amamin
Al-Kadhimin Al-Tbbia Hospital for the period from October 2021to
December 2021. The methods of work included CBC analysis to assess
blood components, ELISA technique to measure protein concentration for
TLR-9, IL-6, and TNF-α, DNA extraction and identification of genetic
variants of the TLR-9 gene by High Resolution Melting (HRM) analysis
method, in addition to sending some samples for DNA sequencing as HRM
results confirmed.
The results showed that there are highly significant differences between
patients and apparently healthy subjects for some blood components such as RBC, HGB, HCT, and PLT, while there are no significant differences in the
number of white blood cells and lymphocytes for patients and healthy people
sequentially.
The immune marker results revealed that there were highly significant
differences between patients and apparently healthy subjects. The mean ±SE
of the TLR9 gene was (2.728± 0.04) (2.219 ±0.06), while IL-6 was (36.24
±0.86), (22.82 ±0.72), and TNF-α was (174.22 ±4.07) (107.98 ±3.25) for
patients and healthy subjects sequentially with p-value 0.0001.
Genotype result clarified that: rs187084 appeared that AG genotype was
common genotype in Iraqi population with odd ratio 12, AA act as a
protective factor (92.9%) with odd ratio 0.07 along with A allele (78.4%).
The rs5743836 result showed AA common genotype (odds ratio 0.26)
while AG and GG may act as a risk factor for predisposition of AML with
an odds ratio of 1.75 and 6.33 respectively.
The rs352140 result revealed GG common genotype among Iraqi
population with odd ratio 0.10 and p-value (0.001) along with G allele may
acting as a prevented fraction of AML (89.8% and 81.5%) respectively. The
odd ratio of GA and AA were 3 and 5.94 sequentially. Haplotype analysis
showed that A A G haplotype was a common haplotype with a higher
frequency (76.2%), an odds ratio of 0.056, and may play a protective role
while G A A and A G G haplotypes with an odds ratio of 11.73 and 6.53
respectively, were may increase the disease risk.
TNF-α, IL-6, and TLR-9 can be used as Immunological biomarkers to
target AML cells, Polymorphisms in the TLR9 genes are linked to AML
susceptibility and may influence disease progression in the Iraqi population.
... Individuals exposed to such high doses of radiation, such as cancer patients receiving radiation therapy or those engaged in nuclear events, should be constantly watched for the possibility of developing ALL as a long-term result of their exposure. [32] Certain chemicals and environmental variables during fetal development, such as benzene, pesticides, and electromagnetic radiation, have been linked to an increased risk of getting ALL. Benzene, a common industrial chemical, has been shown to disturb normal hematopoiesis and increase the incidence of leukemia. ...
Acute lymphocytic leukemia (ALL) is a diverse category of hematological malignancies defined by the clonal proliferation of immature lymphoid cells. While advances in diagnostic procedures and treatment modalities have improved results for many patients, a group of them exhibit clinical characteristics that indicate a high risk of disease progression and unfavorable consequences. Understanding the underlying molecular processes and developing accurate prognostic indicators in this high-risk group is critical for personalized treatment approaches and better patient outcomes. Hematological markers, immunophenotyping profiles, and chromosomal defects in people who were clinically high risk (CHR) for ALL are discussed in this review. Alterations in hematological markers, such as elevated white blood cell counts, decreased hemoglobin levels, and thrombocytopenia, are indicative of the aggressive nature of high-risk ALL. Immunophenotyping investigations revealed abnormal expression patterns of lineage-specific markers, indicating clonal proliferation and differentiation arrest. Furthermore, cytogenetic examination revealed frequent chromosomal defects, such as the Philadelphia chromosome and hyperdiploidy, which have been linked to a poor prognosis in ALL patients. The combination of hematological, immunophenotypic, and cytogenetic data gives a thorough knowledge of disease biology and assists in risk assessment for patients with CHR for ALL. The present review elucidates the intricate interaction of hematological, immunophenotypic, and cytogenetic abnormalities in persons at clinically high risk for ALL, emphasizing the importance of integrated diagnostic techniques to enhance patient outcomes and optimize treatment strategies.
... Despite many epidemiological studies, childhood cancer risk factors and etiology are yet to be fully understood. In previous studies, ionizing radiation in high doses was considered an important risk factor for central nervous system tumors and leukemia [6,7]. Some data also showed a link between childhood cancer and genetic predispositions or the exposition of some chemotherapy agents [8,9]. ...
Background. Cancer is the leading cause of disease-related death among children of more than 1 year of age. However, childhood cancer risk factors and etiology are yet to be fully understood. The goal of this study is to identify geographic variation among children and adolescents diagnosed with pediatric tumors between 2001 and 2018 in the province of Quebec. Methods. We analyzed pediatric patients less than 15 years of age from the Cancer in Young People in Canada (CYP-C) surveillance system who were diagnosed between 2001 and 2018 with cancer in the province of Quebec. The age-standardized age-adjusted incidence rates (AAIR) per 100,000 person years were calculated for all childhood cancers by cancer subgroups, Quebec Health regions, and age groups. Results. Overall, 3904 pediatric patients less than 15 years old were diagnosed with cancer in the province of Quebec in 2001–2018. The overall incidence rate (IR) in the province of Quebec was 16.14 (95%CL [15.56–16.73]) per 100,000 person years. For childhood cancers, regions that presented a higher AAIR were Chaudière-Appalaches and Capitale-Nationale with 18.2 and 17.5 per 100,000 person years, respectively. The incidence rates (IRs) in Chaudière-Appalaches (95% CI 1.0439–1.3532) and in Capitale-Nationale (95% CI 1.0124–1.2942) were statistically higher than the incidence in the province of Quebec (p = 0.0090 and p = 0.0310, respectively). When comparing the AAIR of the CNS tumor subgroup in Chaudière-Appalaches and in Capitale-Nationale, with the provincial average, we noticed a statistically higher incidence in Chaudière-Appalaches and a trend for Capitale-Nationale (p < 0.0001 and p = 0.0602, respectively). Conclusion. There is evidence of spatial clusters in Chaudière-Appalaches and Capitale-Nationale as areas for all childhood cancers. Further studies should be performed to investigate potential risk factors in these regions.
... Cancer ranked as the 2nd leading cause of death in children aged 0-19 years in the United States (US) (American Cancer Society, 2023), with only a few established risk factors including genetic predisposition (5-10% of cases), high-dose ionizing radiation, and prior chemotherapy (IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2012;Spector et al., 2015;Wakeford, 1995Wakeford, , 2013. Previous studies have identified potential environmental risk factors such as parental occupational exposures, pesticides, air pollution and air toxics exposures (Heck et al., 2013b;Lavigne et al., 2017;Malagoli et al., 2016;Rossides et al., 2022;Vinceti et al., 2012;Volk et al., 2019). ...
Background
Maternal solvent exposure has been suspected to increase offspring cancer risk. The study aimed to evaluate the associations between maternal residential exposure to solvents from industrial pollution during pregnancy and childhood cancer.
Methods
The present study included 15,744 cancer cases (aged 0–19 years at diagnosis) identified from California Cancer Registry and 283,141 controls randomly selected from California Birth Registry (20:1 frequency-matched by birth year: 1998–2016). We examined industrial releases of tetrachloroethylene and 1,1,1-trichloroethane within 3 km of the birth address, while we used a 5 km buffer for carbon disulfide. We calculated the total exposure from all linked Toxic Release Inventory sites during each index pregnancy and assigned “ever/never” and “high/low exposed/unexposed” exposure, using median values. We performed quadratic decay models to estimate cancer risks associated with maternal solvent exposure in pregnancy.
Results
1,1,1-Trichloroethane was associated with rhabdomyosarcoma (adjusted Odds Ratio (aOR): 1.96; 95% Confidence Interval (CI): 1.16, 3.32) in the “ever exposed” group. Ever exposure to carbon disulfide was associated with increased risks of medulloblastoma (OR = 1.85, 95% CI 1.01, 3.40) and ependymoma (OR = 1.63 95% CI 0.97, 2.74).
Conclusions
Overall, our findings suggested maternal residential exposure to solvents from industrial sources might be associated with elevated childhood cancer risks.
... for the cancer risk associated with CHD. 3 In this Swedish study, CHD-associated cancers were predominantly in the hematologic system, central nervous system, and head and neck. 3 The underlying causes of the CHD-cancer association were likely to be multifactorial, and shared genetic mutation, 4,5 radiation exposure from medical imaging, [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] and cancer-linked genetic syndromes 4,25 are possible causes. In particular, genetic predispositions, including chromosomal abnormalities, and a single mutation in the DNA (eg, Noonan syndrome) are often found in the pediatric population with CHD 26,27 and are thought to be associated with increased risks of developing cancer. ...
Background
Individuals with genetic syndromes can manifest both congenital heart disease (CHD) and cancer attributable to possible common underlying pathways. To date, reliable risk estimates of hematopoietic cancer (HC) among children with CHD based on large population‐based data remain scant. This study sought to quantify the risk of HC by the presence of genetic syndrome among children with CHD.
Methods and Results
Data sources were the Canadian CHD database, a nationwide database on CHD (1999–2017), and the CCR (Canadian Cancer Registry). Standardized incidence ratios were calculated for comparing HC incidences in children with CHD with the general pediatric population. A modified Kaplan‐Meier curve was used to estimate the cumulative incidence of HC with death as a competing risk. A total of 143 794 children (aged 0–17 years) with CHD were followed up from birth to age 18 years for 1 314 603 person‐years. Of them, 8.6% had genetic syndromes, and 898 HC cases were observed. Children with known syndromes had a substantially higher risk of incident HC than the general pediatric population (standardized incidence ratio, 13.4 [95% CI, 11.7–15.1]). The cumulative incidence of HC was 2.44% (95% CI, 2.11–2.76) among children with a syndrome and 0.79% (95% CI, 0.72–0.87) among children without a syndrome. Acute myeloid leukemia had a higher cumulative incidence during early childhood than acute lymphoblastic leukemia.
Conclusions
This is the first large population‐based analysis documenting that known genetic syndromes in children with CHD are a significant predictor of HC. The finding could be essential in informing risk‐stratified policy recommendations for cancer surveillance in children with CHD.
... Epidemiologic studies have estimated a slightly increased risk of cancer associated with CT radiation exposure in children and adolescents, although there is considerable uncertainty on this topic [21][22][23][24][25][26]. Children are generally considered more vulnerable to the stochastic effects of ionizing radiation because of developing tissues and a longer lifespan for the effects to manifest [27][28][29]. Therefore, it is imperative to always consider the necessity of CT and alternate imaging modalities and to optimize the CT imaging protocols as per the principles of "as low as reasonably achievable" (ALARA) [30]. ...
Purpose
To review the evolution of cross-sectional imaging in pediatric neuroradiology from early developments to current advancements and future directions.
Methods
Information was obtained through a PubMed literature search as well as referenced online resources and personal experience from radiologists currently practicing pediatric neuroimaging and those who experienced the era of nascent cross-sectional imaging.
Results
The advent of computed tomography (CT) and magnetic resonance imaging (MRI) in the 1970s and 1980s brought about a revolutionary shift in the field of medical imaging, neurosurgical and neurological diagnosis. These cross-sectional imaging techniques ushered in a new era by enabling the visualization of soft tissue structures within the brain and spine. Advancements in these imaging modalities have continued at a remarkable pace, now providing not only high high-resolution and 3-dimensional anatomical imaging, but also functional assessment. With each stride forward, CT and MRI have provided clinicians with invaluable insights, improving the accuracy and precision of diagnoses, facilitating the identification of optimal surgical targets, and guiding the selection of appropriate treatment strategies.
Conclusion
This article traces the origins and early developments of CT and MRI, chronicling their journey from pioneering technologies to their current indispensable status in clinical applications and exciting possibilities that lie ahead in the realm of medical imaging and neurologic diagnosis.
... Radiation exposure poses a valid concern, since not only the possibility of stochastic effects but also deterministic levels might be reached [66][67][68]. Children require special attention because they are more sensitive to radiation and have longer lifespans to express changes [69][70][71][72]. A study by Thierry-Chef et al. found that the lifetime risk of brain tumor diagnosis in pediatric patients was Children 2023, 10, 715 9 of 13 estimated to be increased over the normal background rates by 3-40% depending on the dose received, age at exposure, and gender [73]. ...
Pediatric interventional neuroradiology (PINR) is a relatively new field of diagnostic and therapeutic care in the pediatric population that has seen considerable advances in recent decades. However, it is still lagging behind adult interventional neuroradiology due to a variety of reasons, including the lack of evidence validating pediatric-specific procedures, the relative absence of pediatric-specific equipment, and the challenges in establishing and maintaining PINR competencies in a relatively small number of cases. Despite these challenges, the number and variety of PINR procedures are expanding for a variety of indications, including unique pediatric conditions, and are associated with reduced morbidity and psychological stigma. Continued technological advances, such as improved catheter and microwire designs and novel embolic agents, are also contributing to the growth of the field. This review aims to increase awareness of PINR and provide an overview of the current evidence base for minimally invasive neurological interventions in children. Important considerations, such as sedation, contrast agent use, and radiation protection, will also be discussed, taking into account the distinct characteristics of the pediatric population. The review highlights the usefulness and benefits of PINR and emphasizes the need for ongoing research and development to further advance this field.
... Als etablierter Umweltfaktor für Krebserkrankungen im Kindesalter gilt die Exposition durch ionisierende Strahlung (SCHÜZ & ERDMANN 2016). Evidenz für diesen Zusammenhang setzt sich zum einen aus Studien zu Atombombenüberlebenden in Hiroshima und Nagasaki (WALSH & KAISER 2011;RICHARDSON et al. 2009;PRESTON et al. 1994;PRESTON et al. 2004;OZASA et al. 2011;PRESTON et al. 2008) und zum anderen aus einer Vielzahl von Studien zur medizinischen Exposition durch ionisierende Strahlung zusammen (SCHULZE-RATH, HAMMER & BLETTNER 2008;WAKEFORD 2008;WAKEFORD 2013;LITTLE 2008). Die medizinische Anwendung von ionisierender Strahlung und die damit verbundene Forschung lässt sich in zwei Bereiche differenzieren: den Bereich der therapeutischen Anwendung und den Bereich der diagnostischen Anwendung (WAKEFORD 2013). ...
Ziel des hier vorgestellten Forschungsvorhabens war die Prüfung der Machbarkeit einer interdisziplinären Studie zum Zusammenhang zwischen Umwelt- und genetischen Faktoren für das Auftreten von B-Zell ALL im Kindesalter. Im Rahmen einer solchen interdisziplinären Studie soll untersucht werden, ob Kinder mit unterschiedlichen genetischen Subtypen der B-Zell ALL vor Beginn der Erkrankung unterschiedlichen Umweltexpositionen ausgesetzt waren. Im Fokus sollen dabei die Exposition durch ELF-MF und ionisierende Strahlung (IR) durch diagnostische Anwendungen stehen. Zu klären wäre, ob sich die genetischen Strata bezüglich vorangegangener Expositionen bzgl. ELF-MF und niedrig-Dosis IR unterscheiden, wobei auch paternale und maternale Expositionen zu berücksichtigen wären. Bestandteil dieser interdisziplinären Studie wären molekularepidemiologische Ansätze zur Bestimmung genetischer Prädispositionen, Fragebogenerhebungen zu retrospektiven Exposition durch Umweltrisikofaktoren und vor-Ort-Messungen von ELF-MF. Im Rahmen der Machbarkeitsprüfung sollte geklärt werden, ob eine solche interdisziplinäre Studie in eine existierende oder neu beginnende klinische Studie zur pädiatrischen ALL eingebunden werden kann. Die Machbarkeitsstudie sollte wichtige Erkenntnisse zur praktischen Umsetzbarkeit sowie zur statistischen Aussagekraft eines solchen Vorhabens liefern. Auf dieser Basis wurden Empfehlungen für die Durchführung einer interdisziplinären Studie entwickelt.
... En la literatura se han descrito factores de riesgo ambientales implicados en el desarrollo de ci. La relación más fundamentada por la evidencia es la radiación ionizante con la leucemia infantil [26]; sin embargo, fuentes de contaminación como el tráfico vehicular, pesticidas, industrias productoras de solventes orgánicos, plásticos y metales también han mostrado evidencia de asociaciones en diferentes estudios [6,7,27]. ...
Objetivo: Este estudio evaluó el efecto de la proximidad a fuentes industriales de contaminación del aire sobre la aparición de conglomerados de casos de cáncer infantil en
el Área Metropolitana del Valle de Aburrá, del departamento de Antioquia, durante el período 2000-2015. Metodología: La información de casos de cáncer infantil en menores de
15 años residentes del área metropolitana se obtuvo del Registro Poblacional de Cáncer de Antioquia, de dicho periodo. Se identificaron 32 conglomerados industriales, a partir del inventario de la autoridad ambiental local. Se realizaron pruebas de escaneo circular de Kulldorf locales y focalizadas, para detectar conglomerados de cáncer infantil en los municipios y alrededor de los conglomerados industriales respectivamente. Se usó un modelo de regresión multivariable ajustado por estrato socioeconómico, para evaluar el
efecto de las variables espaciales. Resultados: La tasa de incidencia específica en el Valle de Aburrá para el periodo evaluado fue de 117,13 casos por millón de niños menores de 15 años. Las tasas de incidencia más altas se presentaron en los municipios de Medellín y Sabaneta. La prueba de Kulldorf identificó 12 conglomerados espaciales y 8 espaciotemporales con significación estadística en 7 de los municipios, particularmente en Bello y Medellín. Las pruebas focalizadas identificaron conglomerados alrededor de 20 conglomerados industriales. En los modelos multivariables, un conglomerado en Bello evidenció asociación estadísticamente significativa e inversa entre la incidencia y la distancia al conglomerado con direccionalidad sureste. Conclusión: Algunos conglomerados espacio-temporales de cáncer infantil en el Área Metropolitana del Valle de Aburrá entre 2000 y 2015 están relacionados con proximidad a fuentes industriales de contaminación del aire.
... www.nature.com/scientificreports/ Examples are the elevated risk to develop leukaemia after diagnostic CT scans during childhood, as well as the large international nuclear worker study (INWORKS), where repeated and protracted low-dose IR exposures were associated with an elevated leukaemia risk [10][11][12][13][14][15] . The target cells for radiation-induced leukaemia are most likely the HSPCs, since their long-life span allows the accumulation of radiation damage which could compromise their genomic integrity and potentially give rise to leukemogenesis [16][17][18] . ...
The radiosensitivity of haematopoietic stem and progenitor cells (HSPCs) to neutron radiation remains largely underexplored, notwithstanding their potential role as target cells for radiation-induced leukemogenesis. New insights are required for radiation protection purposes, particularly for aviation, space missions, nuclear accidents and even particle therapy. In this study, HSPCs (CD34+CD38+ cells) were isolated from umbilical cord blood and irradiated with 60Co γ-rays (photons) and high energy p(66)/Be(40) neutrons. At 2 h post-irradiation, a significantly higher number of 1.28 ± 0.12 γ-H2AX foci/cell was observed after 0.5 Gy neutrons compared to 0.84 ± 0.14 foci/cell for photons, but this decreased to similar levels for both radiation qualities after 18 h. However, a significant difference in late apoptosis was observed with Annexin-V+/PI+ assay between photon and neutron irradiation at 18 h, 43.17 ± 6.10% versus 55.55 ± 4.87%, respectively. A significant increase in MN frequency was observed after both 0.5 and 1 Gy neutron irradiation compared to photons illustrating higher levels of neutron-induced cytogenetic damage, while there was no difference in the nuclear division index between both radiation qualities. The results point towards a higher induction of DNA damage after neutron irradiation in HSPCs followed by error-prone DNA repair, which contributes to genomic instability and a higher risk of leukemogenesis.
... This together with hereditary effects, represents the longterm stochastic risks of ionizing radiation. The increased risk of malignancy in children, including leukemia and lymphoma, is estimated to 10 −4 /mGy after exposure in utero (9) . The risk to the embryo/fetus depends on: the exposed part of the mother's body, the stage of pregnancy and the absorbed dose. ...
Some of the ethically most sensitive issues in radiation protection arise at imaging of pregnant—and potentially pregnant—patients and of newborn.
This article reviews the current literature and recommendations on imaging during pregnancy and breastfeeding. Risks related to alternative non-ionizing radiation methods are also considered.
With few exceptions, exposure of the fetus through radiography, computed tomography (CT) and nuclear medicine imaging can be limited to safe levels, although studies such as abdominal-pelvic CT cannot avoid significant exposure to fetuses. Eight to 10 weeks post-conception, the fetus has a thyroid which starts to concentrate iodide having crossed the placenta barrier resulting in unacceptably high doses to the fetal thyroid after administration of 131I- and even 123I-iodide and other radiopharmaceuticals with a high content of free radioiodine.
Many radiopharmaceuticals are excreted through breast milk. Breastfeeding interruption recommendations should be followed to keep the effective dose to the infant below 1 mSv.
... The grounds for controversy over the interpretation have been much discussed (Bithell and Stiller 1988;Bithell 1989;MacMahon 1989;Miller 1990;Bithell 1992;Muirhead et al. 1993;Wakeford 1995;Doll and Wakeford 1997;Wakeford et al. 1997aWakeford et al. , 1997bBoice and Miller 1999;Streffer et al. 2003;Wakeford and Little 2003;Brent 2007;UNSCEAR. 2008;Wakeford 2008;Boice 2011;Brent et al. 2013;Wakeford 2013;Brent 2014Brent , 2015Bithell et al. 2018), and as with other studies of medical exposure to radiation for diagnostic purposes, confounding by indication (i.e. selection for a radiographic examination is associated with some factor that predisposes to the disease under study) must be given due consideration. ...
Purpose
For 65 years the interpretation of the statistical association between the risk of cancer in a child and a prior diagnostic X-ray examination of the abdomen of the pregnant mother has been debated. The objections to a direct cause-and-effect explanation of the association vary in their strength, but one of the most notable grounds for controversy is the finding from the first and largest case-control study reporting the association, the Oxford Survey of Childhood Cancers (OSCC), of an almost uniformly raised relative risk (RR) for nearly all of the types of cancer that are most frequent in children. Here we compare the antenatal X-ray associations found in the OSCC for different types of childhood cancer with the results of all other case-control and case-cohort studies appropriately combined in meta-analyses, and we also review the findings of the few cohort studies that have been conducted.
Conclusions
From the case-control/case-cohort studies other than the OSCC there are consistent and clear elevations of risk for all types of childhood cancer combined, all leukaemia, and all cancers except leukaemia combined. This compatibility of the findings of the OSCC with those of the combined other studies is less clear, or effectively absent, when some categories containing smaller numbers of incident cases/deaths are considered, but lack of precision of risk estimates due to sparse data presents inferential challenges, although there is a consistent absence of an association for bone tumours. Further, more recent studies almost certainly address lower intrauterine doses, with an anticipated decrease in estimated risks, which could be misleading when comparisons involve a limited number of studies that are mainly from later years, and a similar problem arises when having to employ all types of antenatal X-ray exposures for a study because data for abdominal exposures are absent. The problem of low statistical power is greater for cohort studies, and this, together with other shortcomings identified in the studies, limits the interpretational value of results. The findings of non-medical intrauterine exposure studies are constrained by sparse data and make a limited contribution to an understanding of the association. Certain aspects of the various studies require a need for caution in interpretation, but overall, the appropriate combination of all case-control/case-cohort studies other than the OSCC lends support to the inference that low-level exposure to radiation in utero proportionally increases the risk of the typical cancers of childhood to around the same level.
... These limitations cannot completely be ruled out but were reduced through the use of data aggregated at a small geographical level [6]. In this context, it is noteworthy that we could not account for several known individual risk factors, including high doses of ionizing radiation received for medical purposes [31], genetic anomalies [32] or high birth weight [33,34]. It seems less likely that these potential individual risk factors have been biasing our estimates because, to the authors' knowledge, their distribution is not expected to be associated with the proximity to the nuclear sites. ...
Background
A previous investigation of the occurrence of childhood acute leukemia around the Belgian nuclear sites has shown positive associations around one nuclear site (Mol-Dessel). In the following years, the Belgian Cancer Registry has made data available at the smallest administrative unit for which demographic information exists in Belgium, i.e. the statistical sector. This offers the advantage to reduce the potential misclassification due to large geographical scales.
Methods
The current study performed for the period 2006–2016 uses Poisson models to investigate (i) the incidence of childhood acute leukemia within 20 km around the four Belgian nuclear sites, (ii) exposure-response relationships between cancer incidence and surrogate exposures from the nuclear sites (distance, wind direction frequency and exposure by hypothetical radioactive discharges taking into account historical meteorological conditions). All analyses are carried out at statistical sector level.
Results
Higher incidence rate ratios were found for children <15 years (7 cases, RR = 3.01, 95% CI: 1.43;6.35) and children <5 years (< 5 cases, RR = 3.62, 95% CI: 1.35;9.74) living less than 5 km from the site of Mol-Dessel. In addition, there was an indication for positive exposure-response relationships with the different types of surrogate exposures.
Conclusion
Results confirm an increased incidence of acute childhood leukemia around Mol-Dessel, but the number of cases remains very small. Random variation cannot be excluded and the ecological design does not allow concluding on causality. These findings emphasize the need for more in-depth research into the risk factors of childhood leukemia, for a better understanding of the etiology of this disease.
... 2017). It can lead to chronic inflammation, which contributes to late tissue injury and increased risk of cancer, and degenerative conditions, including circulatory and neurological disease (Hendry 2001;Robles et al. 2002;Reuter et al. 2010;Schonfeld et al. 2010), in particular when exposure occurs during childhood (Wakeford 2013;Kamiya et al. 2015). ...
The overall aim of this Report is to provide input for the development
of biologically based dose-response (BBDR) models for radiation-
induced cancers and circulatory disease that use an adverse
outcome pathways and key-events approach for providing parameters
for these models. These mechanistic data can be integrated
with the most recent epidemiologic data to develop overall doseresponse
curves for radiation-induced adverse health outcomes.
This integration of the findings from radiation biology and epidemiology
will enhance the risk assessment process by reducing
uncertainties in estimated risk following exposure to low doses and
low dose rates of ionizing radiation.
For many decades the basis for setting radiation protection
guidance for exposure to low absorbed doses and low absorbed-dose
rates of ionizing radiation has been the estimation of the risk of
radiation-induced cancer. In addition, there is ongoing discussion
concerning risks of radiation-induced noncancer effects1 (particularly
circulatory disease). The estimates for radiation-induced cancer
have been derived primarily from exposure to higher doses and
higher dose rates of ionizing radiation and assumptions on how to
extrapolate to low doses and low dose rates. For the purpose of this
Report, for low linear-energy transfer (LET) radiation, a low
absorbed dose is <100 mGy delivered acutely, and a low absorbeddose
rate is <5 mGy h–1 for any accumulated absorbed dose (NCRP
2015).
This Report addresses the conclusions and recommendations
from three previous National Council on Radiation Protection and
Measurements (NCRP) reports and commentaries on the topic of
the risks of adverse health outcomes at low doses and low dose
rates of ionizing radiation (NCRP 2012, 2015, 2018a). In this context,
the present Report proposes a path forward to enhance the
estimation of risk at low doses and low dose rates. Such a modified
approach is needed to supplement the information that can be
obtained from the conduct of even large epidemiologic studies such
as the One Million U.S. Workers and Veterans Study of Low-Dose
Radiation Health Effects (million U.S. workers and veterans study)
1For this Report the term noncancer is restricted to somatic noncancer
outcomes and does not include heritable effects.
(Bouville et al. 2015; Boice et al. 2019), the International Nuclear
Workers Study (Leuraud et al. 2015; Richardson et al. 2015), the
European pooled study of radiation-induced cancer from pediatric
computed tomography (Bernier et al. 2019), or other low-dose pooling
studies (Lubin et al. 2017; Little, Kitahara et al. 2018). This
Report presents such an approach based upon the integration of
data from epidemiology and radiation biology.
An essential component of the integration process is the use of
BBDR models with parameters being developed from analyzing
adverse outcome pathways and their associated key events. In
principle, an adverse outcome pathway is the series of necessary
steps that result in an initial molecular event leading to an adverse
health outcome (for this Report, either cancer or circulatory disease).
Definitions of adverse outcome pathways and key events are
given in Section 2 and can be found also in recent reviews (Edwards
et al. 2016; Preston 2017).
Also, when considering mechanistic data underlying the induction
of adverse health outcomes, it is important to distinguish
between potential bioindicators and biomarkers of these outcomes.
A bioindicator is a cellular alteration that is on a critical pathway
to the disease endpoint itself (i.e., necessary, but not by itself sufficient
for the endpoint), such as a specific mutation in a target cell
that is associated with tumor formation. Thus, a bioindicator can
be perceived as informing on the shape of the dose-response curve
for the disease outcome or on cancer frequency itself, and therefore,
is equivalent to a key event. A biomarker is a biological phenotype
[e.g., chromosome alteration, deoxyribonucleic acid (DNA) adduct,
gene expression change, specific metabolite] that can be used to
indicate a response to an exposure at the cell or tissue level. In this
regard, a biomarker is generally a measure of the potential for
development of an adverse health outcome such as cancer (e.g., a
predictor of exposure level).
This Report expands upon this general approach of adverse outcome
pathways, key events, and BBDR models to enhance the process
of low-dose, low dose-rate risk estimation. The arrangement
of this Report for the application of this general approach is: here
is what we know, here is what we need to know, and this is how
we can obtain the necessary knowledge. A synopsis of Sections 2
through 7 is given below.
Section 2 (Introduction) provides an overview of current
approaches to radiation risk assessment, the associated uncertainties
and possible ways forward for enhancing the estimation of
risks of cancer and circulatory disease at low doses and low dose
rates.
Section 3 (Epidemiology, Biosamples and Biomarkers: Cancer
and Circulatory Disease) presents a review of the radiation epidemiologic
studies for which biomarker data or biological samples
were used. For noncancer effects it was clear that the only adverse
health outcome for which significant data from radiation biology
are available for use in BBDR models is circulatory disease and
so this forms the basis for the discussion on noncancer effects.
There are a large number of radiation epidemiologic studies available
that are very informative for estimating risks at higher doses
but that can only be used with a fairly high degree of uncertainty
for predicting low-dose risks. A review of the main radiation epidemiologic
studies has been provided in NCRP Commentary No. 27
(NCRP 2018a).
Section 3.1 briefly describes the major epidemiologic radiation
studies with associated biosamples that potentially can be
employed to conduct investigations of bioindicators of the pathogenesis
of radiation-induced cancer and other health endpoints.
While none of the current investigations has yet been able to identify
definitive bioindicators, there are several suggestions of biomarkers
that merit confirmation through further investigations
and might be informative in the absence of more definitive bioindicator
studies. The details and references for these studies are provided
in Section 3.1.3.
Section 3.2 indicates that it is likely that bioindicators of radiation-
induced noncancer effects at low doses will be restricted to
circulatory disease and so this is the sole topic reviewed for biomarkers
associated with noncancer responses. With current knowledge,
substantive biomarker information is only available in two
major radiation studies: the Japanese atomic-bomb survivors, and
the Mayak Production Association workers (Mayak workers),
although little use has been made of this latter population in analyses
to date.
In summary, there is a paucity of radiation-specific bioindicators
of cancer and circulatory disease and a relative lack of radiation-
specific biomarkers predictive of adverse health outcomes.
Thus, it is necessary to consider the mechanisms of formation of
cancers and circulatory disease, especially for radiation-induced
responses, to aid with the identification of bioindicators of adverse
health outcomes and to a lesser extent, biomarkers of association
with an adverse health outcome.
Section 4 (Radiation-Induced Biological Effects Related to Cancer
and Circulatory Disease) reviews the underlying mechanisms
of carcinogenesis and circulatory disease with the aim of identifying
potential bioindicators of the adverse health outcome, and if
possible radiation-associated bioindicators of such responses. There
has been an increased understanding of the underlying mechanisms
of human diseases as a result of new molecular, cellular and
computational approaches, further enhanced by informative experimental
animal systems that model human disease. To a lesser
extent such approaches have been used to better understand the
etiology of radiation-induced diseases. There is a description of
the types of studies that have identified pathways and potential
key events in the carcinogenesis process (Section 4.1).
While currently there are no fully validated bioindicators or biomarkers
of radiation-induced cancer, there is a substantial and
increasing body of knowledge on radiation-induced cancer mechanisms,
particularly in experimental animal systems. Quantification
of inflammation and generation of persistently elevated reactive
oxygen species (ROS) holds promise as a further bioindicator that
is also recognized as an enabling hallmark of cancer in the context
of Hanahan and Weinberg (2011). In addition, cell-survival parameters
can be of importance in mechanistic models of carcinogenesis.
The use of data from experimental animal systems provides
opportunities to demonstrate the added value of building and
applying mechanistic models of radiation-induced cancer. There are
additional opportunities to apply similar models in some human
radiation-induced cancers, most notably thyroid, where some work
utilizing knowledge of the CLIP2 marker is already available. The
incorporation of quantitative mechanistic data into appropriate
cancer models (discussed in Sections 5 and 6) is likely to increase
the precision of estimated risks, particularly at low-dose levels and
so continued efforts to identify and validate bioindicators of radiation-
induced cancers will assist in refining risk estimation.
Section 4.2 outlines the biology of circulatory disease, a significant
radiation-induced noncancer disease2 and the one which currently
offers the best opportunity for bioindicator identification
given the mechanistic data already available. The complex inflammatory
processes underlying most major types of circulatory disease
are reviewed, specifically those associated with atherosclerosis.
The possible ways that low-dose radiation exposure and other
2NCRP (2018a) stated that radiation-induced cardiovascular disease
(a circulatory disease) remains an area where further investigation is necessary.
Although there is evidence that cardiovascular disease may be a
factor at exposures lower than previously estimated, that evidence was
not yet sufficient to allow for development of an approach to including cardiovascular
disease in NCRP’s overall system of radiation protection published
in NCRP (2018b).
biological stressors might affect the circulatory system are also
reviewed. While it is not possible yet to identify bioindicators of
radiation-induced circulatory disease, it appears feasible to build
upon the rapidly increasing knowledge of the mechanisms of formation
of circulatory disease to develop adverse outcome pathways
and at least some of the associated key events.
Section 5 (Biologically Based Dose-Response Models) assesses
biomathematical models of chronic disease, especially those for
cancer and circulatory disease (with particular emphasis in circulatory
disease on models of atherosclerosis). First, general material
outlining the overall goals of biomathematical models is presented,
followed by discussion of modeling considerations, particularly
application of specific models using human, animal or cell data to
cancer and circulatory disease. Biologically based modeling of radiation-
induced cancers of the breast, colon, lung, and thyroid gland
have been conducted.
After considerations of some general features of BBDR models of
cancer development in Section 5.1, a number of BBDR models and
their application to various human and animal datasets are presented
in Section 5.2. Despite some shortcomings (e.g., the fact that
different models might explain the available data using different
mechanistic assumptions), multiple pathway models are considered
a promising conceptual approach to developing a general model
framework for the complex process of carcinogenesis in various tissues.
In certain cases, multiple pathway models may allow predictions
that can be validated against experimental data.
Circulatory disease models are considered in Section 5.3. These
are less well developed than those that have been constructed
to model cancer. A number of candidate models of atherosclerosis
are considered. Atherosclerosis is the disease process underlying
the main types of circulatory disease, specifically ischemic heart
disease (IHD) and stroke, which is thought to have a largely inflammatory
etiology. A number of atherosclerosis models, which share
certain features, have been proposed for these inflammatory
processes, specifically the adhesion and transport of monocytes
through the epithelial cell layer, and diffusion through the intima.
However, it is not yet clear what the radiation-associated mechanisms
may be for most types of circulatory disease.
Having identified the types of BBDR models that could possibly
be used to enhance the estimation of low-dose, low dose-rate radiation
adverse health outcomes, it is necessary to determine whether
there is a generalized model that can be used for: all radiationinduced
cancer types, or circulatory disease as a class.
It was concluded that it would be unlikely that a single model
structure could be used for describing cancer and circulatory disease.
Also, it appears likely that there may be different responses
even for different types of circulatory disease.
The concept of a generalized model is discussed in Section 6
(Proposed Generalized Model Framework of Cancer and Circulatory
Disease). It is proposed that a form of multistage clonal expansion
model would be appropriate for integrating data from epidemiology
and radiation biology for estimating low-dose, low dose-rate
cancer risk. The parameters for such a model structure are proposed
to be developed from an adverse outcome pathways and
key-events approach. In such an approach the key events are considered
to be bioindicators of the adverse health outcome itself. In
support of this proposal to utilize generalized multistage clonal
expansion models, there has been considerable recent discussion on
the use of such parameterized models for environmental chemicals
(OECD 2020). The Organization for Economic Co-operation and
Development (OECD 2020) website provides a considerable amount
of information on developing adverse outcome pathways and their
use in risk assessment and ultimately in risk management practice.
This general approach is also described and applied in the
research program of the U.S. Environmental Protection Agency
(EPA 2018).
A description of biologically detailed models of specific cancers
that have been applied with some levels of success is provided to
indicate the viability of the use of BBDR models for estimating
adverse health outcomes at low doses and low dose rates. While not
definitive at this time, the approach certainly has a real likelihood
of being successful.
Section 7 (Research Needs) provides specific examples of
research activities, both large and small that are designed for
developing adverse outcome pathways and their associated key
events. These include epidemiologic, human sample, laboratory
animal, cellular, and molecular studies. Such research activities
include investigating some general but critical responses, in order
to derive greater insight into the parameters of most importance
for further model development. Currently, one can envisage the following
to be of high relevance:
• target cell population numbers and characteristics;
• survival parameters for these populations after radiation
exposure;
• target gene(s) critical for pathogenesis and their mutation
or epimutation frequency as a function of radiation dose;
• proliferation characteristics in normal and mutation-carrying
cell populations; and
• timing and frequency of acquisition of further mutational
events in key genes and the impact of these on survival and
proliferation characteristics.
For enhanced model development, it is necessary to more fully
identify the mechanisms of cancer development in response to radiation.
The following are of importance in this regard:
• Mechanisms in the development of a radiation-induced disease
may differ from those in sporadic disease.
• Does radiation initiate or accelerate the same processes that
lead to sporadic disease, or are distinct molecular pathways
involved?
• BBDR models have the potential to address such questions
if appropriate bioindicators become available for specific
types of cancer or other diseases.
• For transcriptomics, proteomics, metabolomics and epigenomics,
adequate BBDR models ideally might require measurements
at several time points because the profiles of
phenotypic alterations may differ by stage in the pathogenesis
of a disease.
Clearly, the overarching need is the furthering of research targeted
at the underlying mechanisms of radiation-induced adverse
health outcomes (cancer and noncancer disease) leading to the
identification of truly informative bioindicators of the apical endpoint
(i.e., the adverse health outcome). The framework for such an
approach can be the characterization of adverse outcome pathways
for specific outcomes and the identification of key events from the
initial event to adverse health outcome. In this context, a key-event
or informative bioindicator is a true surrogate for the adverse
health outcome. This approach will require the integration of data
from epidemiology and radiation biology to maximize the information
for estimating low-dose responses for adverse health outcomes.
A particularly important result will be the ability to better describe
the form of the dose-response curve for different types of radiation-
induced cancer, for example, and thereby avoid the need to rely
on application of the linear-nonthreshold (LNT) model without sufficient
biological substantiation. A concerted effort will be needed;
this is going to require a well-defined and quite extensive research
effort. The need for this effort is recognized by many in the risk
assessment and risk management arena.
... The occurrence of epidemics of infections disease has been related to space-time clustering of leukemia and other childhood cancers [37,38]. For leukemia and central nervous system tumors, ionizing radiation in high doses is the only environmental exposure established as a risk factor in the literature [39], while others remained under study such as exposure pesticides, volatile organic compounds such as benzene, and traffic-related air pollution [35,[40][41][42]. ...
Background:
Leukemia is the most common cancer in childhood. The estimated incidence rate of childhood leukemia in Colombia is one of the highest in America and little is known about its spatial distribution.
Purpose:
To explore the presence of space-time clustering of childhood leukemia in Colombia.
Methods:
We included children less than 15 years of age with confirmed diagnosis of acute leukemia reported to the national surveillance system for cancer between 2009 and 2017. Kulldorff's spatio-temporal scan statistics were used with municipality and year of diagnosis as units for spatial and temporal analysis.
Results:
There were 3846 cases of childhood leukemia between 2009 and 2017 with a specific mean incidence rate of 33 cases per million person-years in children aged 0-14 years. We identified five spatial clusters of childhood leukemia in different regions of the country and specific time clustering during the study period.
Conclusion:
Childhood leukemia seems to cluster in space and time in some regions of Colombia suggesting a common etiologic factor or conditions to be studied.
... Childhood leukaemia is a rare cancer and the only established environmental risk factor is ionising radiation in high doses (Wakeford, 2013). The childhood leukaemia example is of particular interest, as there have been a number of reports of childhood leukaemia clusters in the literature (McNally and Eden, 2004). ...
The main goal of disease mapping is to estimate disease risk and identify high-risk areas. Such analyses are hampered by the limited geographical resolution of the available data. Typically the available data are counts per spatial unit and the common approach is the Besag-York-Mollié (BYM) model. When precise geocodes are available, it is more natural to use Log-Gaussian Cox processes (LGCPs). In a simulation study mimicking childhood leukaemia incidence using actual residential locations of all children in the canton of Zürich, Switzerland, we compare the ability of these models to recover risk surfaces and identify high-risk areas. We then apply both approaches to actual data on childhood leukaemia incidence in the canton of Zürich during 1985-2015. We found that LGCPs outperform BYM models in almost all scenarios considered. Our findings suggest that there are important gains to be made from the use of LGCPs in spatial epidemiology.
... As mentioned in the MELODI strategic research agenda (Kreuzer et al. 2018a) and the HLEG report (HLEG 2009), differences in radiation susceptibility between individuals, or groups, may relate to genetic constitution (determining sex and other phenotypic features), but also to other characteristics such as age at exposure, attained age, health status and comorbidity, epigenetic factors, lifestyle, and co-exposures to other (non-radiological) stressors. Age at exposure clearly affects the radiation-induced risk of certain cancers, such as for instance leukemia (Wakeford 2013) or thyroid cancer (Cardis et al. 2005), for which exposure at younger ages are associated with higher radiation related-risks (expressed as excess relative risk per Gy). Whether such patterns apply to all cancer types is, however, uncertain (UNSCEAR 2013). ...
Purpose: To summarize existing knowledge and to understand individual response to radiation exposure, the MELODI Association together with CONCERT European Joint Programme has organized a workshop in March 2018 on radiation sensitivity and susceptibility.
Methods: The workshop reviewed the current evidence on this matter, to inform the MELODI Strategic Research Agenda (SRA), to determine social and scientific needs and to come up with recommendations for suitable and feasible future research initiatives to be taken for the benefit of an improved medical diagnosis and treatment as well as for radiation protection.
Results: The present paper gives an overview of the current evidence in this field, including potential effect modifiers such as age, gender, genetic profile, and health status of the exposed population, based on clinical and epidemiological observations.
Conclusion: The authors conclude with the following recommendations for the way forward in radiation research: (a) there is need for large (prospective) cohort studies; (b) build upon existing radiation research cohorts; (c) use data from well-defined cohorts with good exposure assessment and biological material already collected; (d) focus on study quality with standardized data collection and reporting; (e) improve statistical analysis; (f) cooperation between radiobiology and epidemiology; and (g) take consequences of radiosensitivity and radiosusceptibility into account.
... One established environmental risk factor is ionising radiation [3,4]. Evidence for this mainly comes from studies of atomic bomb survivors in Hiroshima and Nagasaki [5,6] and a variety of studies on medical exposure to ionising radiation [7]. ...
Studies on children exposed to ionizing radiation by computed tomography (CT) indicate an increased risk of leukemia and central nervous system (CNS) tumors. Evidence of the risks associated with diagnostic X-ray examinations, the most frequent examination in pediatric radiology, in which the radiation dose is up to 750 times lower compared to CT examinations, is less clear.
This study presents results of the second follow-up for the risk of childhood cancer in a cohort of children (<15 years) with diagnostic X-ray exposure at a large German hospital during 1976-2003 followed for additional 10 years until 2016.
With a latency period of six months, 92,998 children contributed 794,549 person-years. The median effective dose was 7 μSv. 100 incident cancer cases were identified: 35 leukemia, 13 lymphomas, 12 CNS tumors, 15 blastomas, 15 sarkomas and 10 other solid tumors, consisting of six germ cells tumors, three thyroid cancers and one adrenocortical carcinoma. For all cancer cases combined the standardized incidence ratio (SIR) was 1.14 (95% confidence interval (CI) 0.93-1.39), for leukemia 1.15 (95% CI 0.63-1.61), for lymphomas 1.03 (95% CI 0.55-1.76), for CNS tumors 0.65 (95% CI 0.34-1.14), for blastomas 1.77 (95% CI 0.91-2.91), for sarkomas 1.28 (95% CI 0.71-2.11) and for other solid tumors 2.38 (95% CI 1.14-4.38). Dose-response analysis using Poisson regression revealed no trend for dose groups. Results did not differ substantially with a latency period of two years for all cancer entities and five years for solid tumors in sensitivity analyses.
Overall, the null results of the first follow-up were confirmed. Although an association between radiation exposure and a risk for certain solid tumors like thyroid cancer is known, the significantly increased SIR in the group of other solid tumors must be critically interpreted in the context of the small number of cases and the very low doses of radiation exposure in this group.

.
... Even though the increased tube current to compensate for the higher noise level at 80 kVp, the measured noise values were still greater with the 80-kVp CT scans than those observed in the 120-kVp CT scans. 13 Furthermore, the gray-white matter contrast-to-noise ratio was still increased at 80-kVp CT despite the increased noise value, and there was no significant difference in overall image quality scores between 80-and 120-kVp scans. Secondly, various kinds of surgical materials and devices may introduce substantial beam hardening artifacts (e.g., streak or metallic artifacts), which are often more severe at lower tube voltage than at high tube potential. ...
... Children and young adults are more sensitive to the stochastic effects of ionizing radiation because their young bodies undergo rapid cell division. Furthermore, the relatively long remaining life span of children and young adults leaves ample time for expression of potential radiation effects compared with that of adults (1,(11)(12)(13). In addition, children receive higher effective doses because of their smaller body size if dedicated pediatric CT protocols are not applied. ...
Given the growing awareness of and concern for potential carcinogenic effects of exposure of children to ionizing radiation at CT, optimizing acquisition parameters is crucial to achieve diagnostically acceptable image quality at the lowest possible radiation dose. Among currently available dose reduction techniques, recent technical innovations have allowed the implementation of low tube voltage scans and iterative reconstruction (IR) techniques into daily clinical practice for pediatric CT. The benefits of lowering tube voltage include a considerable reduction in radiation dose and improved contrast on images, especially when an iodinated contrast medium is used. The increase in noise, which is attributed to decreased photon penetration, is a major drawback but is not as severe as that at adult CT because of the small body size of children. In addition, use of IR algorithms can suppress increased noise, yielding wider applicability for low tube voltage scans. However, a careful implementation strategy and methodologic approach are necessary to maximize the potential for dose reduction while preserving diagnostic image quality under each clinical condition. The potential pitfalls of and topics related to these techniques include (a) the effect of tube voltage on the surface radiation dose, (b) the effect of window settings, (c) accentuation of metallic artifacts, (d) deterioration of low contrast detectability at low-dose settings, (e) interscanner variation of x-ray spectra, and (f) a comparison with the use of a spectral shaping technique. Appropriate use of low tube voltage and IR techniques is helpful for radiation dose reduction in most applications of pediatric CT. Online DICOM image stacks are available for this article . ©RSNA, 2018.
Objectives
To investigate the feasibility of pediatric 18F-FDG total-body PET/CT imaging with an ultra-low activity and explore an optimized acquisition time range.
Methods
A total of 38 pediatric patients were prospectively enrolled and underwent dynamic total-body PET/CT imaging using ultra-low 18F-FDG activity (0.37 MBq/kg). The 60-minute list-mode raw data were acquired and then reconstructed as static PET images by using 50–51, 50–52, 50–53, 50–54, 50–55, 50–58, 50–60, and 45–60 minutes data, which were noted as G1, G2, G3, G4, G5, G8, G10, and G15, respectively. Image qualities were subjectively evaluated using the Likert scale and were objectively evaluated by the quantitative metrics including standard uptake value (SUV), signal-to-noise ratio (SNR), target-to-background ratio (TBR), and contrast-to-noise ratio (CNR).
Results
The injected activity of FDG was 13.38 ± 5.68 MBq (4.40–28.16 MBq) and produced 0.58 ± 0.19 mSv (0.29–1.04 mSv) of effective dose. The inter-reader agreement of subjective image quality was excellent (kappa = 0.878; 95% CI, 0.845–0.910). The average scores of image quality for G1–G15 were 1.10 ± 0.20, 2.03 ± 0.26, 2.66 ± 0.35, 3.00 ± 0.27, 3.32 ± 0.34, 4.25 ± 0.30, 4.49 ± 0.36, and 4.70 ± 0.37, respectively. All image scores are above 3 and all lesions are detectable starting from G8. SNRs of backgrounds, TBRs, and CNRs were significant differences from the control group before G8 (all P < 0.05).
Conclusion
The image quality of the 8 min acquisition for pediatric 18F-FDG total-body PET/CT with an ultra-low activity could meet the diagnostic requirements.
Advances in knowledge
This study confirms the feasibility of ultra-low dose PET imaging in children, and its methods and findings may guide clinical practice. pediatric patients will benefit from reduced radiation doses.
By the beginning of the year 2021, the estimated number of new cancer cases worldwide was about 19.3 million and there were 10.0 million cancer-related deaths. Cancer is one of the deadliest diseases worldwide that can be attributed to genetic and environmental factors, including nutrition. The good nutrition concept focuses on the dietary requirements to sustain life. There is a substantial amount of evidence suggesting that a healthy diet can modulate cancer risk, particularly the risk of colorectal and breast cancers. Many studies have evaluated the correlation between our diet and the risk of cancer development, prevention, and treatment. The effect of diet on cancer development is likely to happen through intertwining mechanisms including inflammation and immune responses. For instance, a greater intake of red and processed meat along with low consumption of fruits and vegetables has been associated with increased levels of inflammatory biomarkers that are implicated in cancer development. On the other hand, the consumption of phytosterols, vitamins, and minerals, which exert antioxidant and anti-inflammatory roles have been linked to lower cancer risk, or even its occurrence prevention. In this book, we aim to summarize the current knowledge on the role of nutrition in cancer to provide the best scientific advice in this regard.
B‐cell Acute Lymphoblastic Leukemia (B‐ALL) is the most common pediatric cancer, arising most often in children aged 2–5 years. This distinctive age distribution hints at an association between B‐ALL development and disrupted immune system function during a susceptible period during childhood, possibly triggered by early exposure to infection. While cure rates for childhood B‐ALL surpass 90% in high‐income nations, survivors suffer from diminished quality of life due to the side effects of treatment. Consequently, understanding the origins and evolution of B‐ALL, and how to prevent this prevalent childhood cancer, is paramount to alleviate this substantial health burden. This article provides an overview of our current understanding of the etiology of childhood B‐ALL and explores how this knowledge can inform preventive strategies.
Purpose:
The purpose of this paper is to provide an overview of the methodology used to estimate radiation genetic risks and quantify the risk of hereditary effects as outlined in the ICRP Publication 103. It aims to highlight the historical background and development of the doubling dose method for estimating radiation-related genetic risks and its continued use in radiological protection frameworks.
Results:
This article emphasizes the complexity associated with quantifying the risk of hereditary effects caused by radiation exposure and highlights the need for further clarification and explanation of the calculation method. As scientific knowledge in radiation sciences and human genetics continues to advance in relation to a number of factors including stability of disease frequency, selection pressures, and epigenetic changes, the characterization and quantification of genetic effects still remains a major issue for the radiological protection system of the International Commission on Radiological Protection.
Conclusion:
Further research and advancements in this field are crucial for enhancing our understanding and addressing the complexities involved in assessing and managing the risks associated with hereditary effects of radiation.
When planning to undertake paraclinical investigations in pregnancy that involve ionizing radiation, a specialist should always think of the most appropriate test or intervention that carries minimal risks to both mother and fetus. A fetal radiation dose well below 50 mGy will be obtained in most cases. The risks of lethality, genetic damage/epigenetic change, teratogenicity, growth impairment or sterility are almost inexistent at this dose. Looking at the literature, one can see that old papers have shown an increased risk for malignancy, but this hasn’t been proven by the more recent studies. The linear no-threshold rule has been contradicted by recent scientific data with regards to malignancy risk. The same applies for iodinated mediums used as contrast. With the recent advances in medicine and the high expectations from the pregnant population, it has become obvious that in our days imaging in pregnancy is something that is frequently used. It is important to know what investigations can be performed in pregnancy with minimal effects on the fetus. A review of the literature has shown that the effects of a radiation below 50 mGy are likely to be negligible in pregnancy, with minimal or none risks in regards to the fetus. Magnetic resonance imaging (MRI) is the investigation of choice when it comes to pregnancy. The informed consent should always be sought and, when possible, the written consent.
B-cell acute lymphoblastic leukemia (B-ALL) stands as the primary contributor to childhood cancer-related mortality on a global scale. The development of the most conventional forms of this disease has been proposed to be conducted by two different steps influenced by different types of risk factors. The first step is led by a genetic insult that is presumably acquired before birth that transforms a healthy cell into a preleukemic one, which is maintained untransformed until the second step takes place. This necessary next step to leukemia development will be triggered by different risk factors to which children are exposed after birth. Murine models that recap the stepwise progression of B-ALL have been instrumental in identifying environmental and genetic factors that contribute to disease risk. Recent evidence from these models has demonstrated that specific environmental risk factors, such as common infections or gut microbiome dysbiosis, induce immune stress, driving the transformation of preleukemic cells, and harboring genetic alterations, into fully transformed leukemic cells. Such models serve as valuable tools for investigating the mechanisms underlying preleukemic events and can aid in the development of preventive approaches for leukemia in child. Here, we discuss the existing knowledge, learned from mouse models, of the impact of genetic and environmental risk factors on childhood B-ALL evolution and how B-ALL prevention could be reached by interfering with preleukemic cells.
Background:
Many high-dose groups demonstrate increased leukaemia risks, with risk greatest following childhood exposure; risks at low/moderate doses are less clear.
Methods:
We conducted a pooled analysis of the major radiation-associated leukaemias (acute myeloid leukaemia (AML) with/without the inclusion of myelodysplastic syndrome (MDS), chronic myeloid leukaemia (CML), acute lymphoblastic leukaemia (ALL)) in ten childhood-exposed groups, including Japanese atomic bomb survivors, four therapeutically irradiated and five diagnostically exposed cohorts, a mixture of incidence and mortality data. Relative/absolute risk Poisson regression models were fitted.
Results:
Of 365 cases/deaths of leukaemias excluding chronic lymphocytic leukaemia, there were 272 AML/CML/ALL among 310,905 persons (7,641,362 person-years), with mean active bone marrow (ABM) dose of 0.11 Gy (range 0-5.95). We estimated significant (P < 0.005) linear excess relative risks/Gy (ERR/Gy) for: AML (n = 140) = 1.48 (95% CI 0.59-2.85), CML (n = 61) = 1.77 (95% CI 0.38-4.50), and ALL (n = 71) = 6.65 (95% CI 2.79-14.83). There is upward curvature in the dose response for ALL and AML over the full dose range, although at lower doses (<0.5 Gy) curvature for ALL is downwards.
Discussion:
We found increased ERR/Gy for all major types of radiation-associated leukaemia after childhood exposure to ABM doses that were predominantly (for 99%) <1 Gy, and consistent with our prior analysis focusing on <100 mGy.
Objectives:
To compare the diagnostic and staging efficacy of PET/diagnostic-level CT (PET/DxCT) and PET/low-dose CT (PET/LDCT) in pretreatment pediatric lymphoma patients and to estimate the reduction of the CT effective dose in the PET/CT scan.
Methods:
One hundred and five pediatric patients who underwent total-body PET/CT examination were enrolled and divided into the DxCT group (n = 47) and LDCT group (n = 58) according to their dose levels. The sensitivity, specificity, PPV, and NPV of PET/DxCT and PET/LDCT for detecting the involvement of lymph node, spleen, bone marrow, and other extranodal organs in pretreatment lymphoma were compared. ROC analysis was performed to evaluate the integral efficiency. The staging accuracies based on PET/DxCT and PET/LDCT were also evaluated. Dosimetry was calculated for DxCT and LDCT, and the reduction in the effective dose was estimated.
Results:
In the diagnosis of nodal, splenic, bone marrow, and other extranodal involvement, the differences in sensitivity, specificity, PPV, and NPV between PET/LDCT and PET/DxCT were not significant (all p values ∈ [0.332, 1.000]). Both modalities had accuracies above 90% and the ROC analysis indicated good or high efficiency in diagnosing all patterns of lymphoma involvement. PET/LDCT and PET/DxCT each had a staging accuracy of 89.7% and 89.4%, respectively. LDCT had a comparable image quality score with DxCT, with a significant increase in noise (p < 0.001) and a 66.1% reduction in effective dose.
Conclusions:
PET/LDCT allowed for a 66.1% CT effective dose reduction compared to PET/DxCT in pediatric lymphoma patients without compromising the diagnostic and staging efficacy.
Key points:
• Pediatric lymphoma patients can benefit from a reduced effective dose of PET/CT. • This retrospective study showed that the diagnostic and staging efficacies of PET/low-dose CT are comparable to those of PET/diagnostic-level CT, both with satisfactory efficiency in diagnosing all patterns of lymphoma involvement. • PET/low-dose CT allowed for a 66.1% CT effective dose reduction compared to PET/diagnostic-level CT.
Over the past several decades, the incidence of early-onset cancers, often defined as cancers diagnosed in adults <50 years of age, in the breast, colorectum, endometrium, oesophagus, extrahepatic bile duct, gallbladder, head and neck, kidney, liver, bone marrow, pancreas, prostate, stomach and thyroid has increased in multiple countries. Increased use of screening programmes has contributed to this phenomenon to a certain extent, although a genuine increase in the incidence of early-onset forms of several cancer types also seems to have emerged. Evidence suggests an aetiological role of risk factor exposures in early life and young adulthood. Since the mid-20th century, substantial multigenerational changes in the exposome have occurred (including changes in diet, lifestyle, obesity, environment and the microbiome, all of which might interact with genomic and/or genetic susceptibilities). However, the effects of individual exposures remain largely unknown. To study early-life exposures and their implications for multiple cancer types will require prospective cohort studies with dedicated biobanking and data collection technologies. Raising awareness among both the public and health-care professionals will also be critical. In this Review, we describe changes in the incidence of early-onset cancers globally and suggest measures that are likely to reduce the burden of cancers and other chronic non-communicable diseases.
This article attempts to put the Ukrainian conflict in the wider context of nuclear weapons possession and potential use, to point out how its conduct should affect public perception of such use, and the urgency for effective nuclear arms control measures including a determined resolve to implement the United Nations' 2017 Treaty on the Prevention of Nuclear Weapons.
The primary aim of this study was to determine the degree to which a multivariable principal component model based on several potentially carcinogenic metals and pesticides could explain the county‐level pediatric cancer rates across Idaho. We contend that human exposure to environmental contaminants is one of the reasons for increased pediatric cancer incidence in the United States. Although several studies have been conducted to determine the relationship between environmental contaminants and carcinogenesis among children, research gaps exist in developing a meaningful association between them. For this study, pediatric cancer data was provided by the Cancer Data Registry of Idaho, concentrations of metals and metalloids in groundwater were collected from the Idaho Department of Water Resources, and pesticide use data were collected from the United States Geological Survey. Most environmental variables were significantly intercorrelated at an adjusted P‐value <0.01 (97 out of 153 comparisons). Hence, a principal component analysis was employed to summarize those variables to a smaller number of components. An environmental burden index (EBI) was constructed using these principal components, which categorized the environmental burden profiles of counties into low, medium, and high. EBI was significantly associated with pediatric cancer incidence (P‐value <0.05). The rate ratio of high EBI profile to low EBI profile for pediatric cancer incidence was estimated as 1.196, with lower and upper confidence intervals of 1.061 and 1.348, respectively. A model was also developed in the study using EBI to estimate the county‐level pediatric cancer incidence in Idaho (Nash‐Sutcliffe Efficiency = 0.97).
Simple Summary
Leukemia is the most common type of cancer among children worldwide. The aim of this umbrella review was to provide an evidence-based summary of epidemiological studies on environmental risk factors and the risk of childhood acute lymphoblastic leukemia (ALL), by exposure window. Second aim was to assess the prevalence in the German population which determines the relevance on population level. Only low doses of ionizing radiation in early childhood and maternal exposure to general pesticides during pregnancy showed convincing evidence of an association with childhood ALL. Other risk factors vary in level of association. The results of this umbrella review should be interpreted with caution; as the evidence are mostly from case-control studies, where selection and recall bias are potential concerns.
Abstract
Leukemia is the most common type of cancer among children and adolescents worldwide. The aim of this umbrella review was (1) to provide a synthesis of the environmental risk factors for the onset of childhood acute lymphoblastic leukemia (ALL) by exposure window, (2) evaluate their strength of evidence and magnitude of risk, and as an example (3) estimate the prevalence in the German population, which determines the relevance at the population level. Relevant systematic reviews and pooled analyses were identified and retrieved through PubMed, Web of Science databases and lists of references. Only two risk factors (low doses of ionizing radiation in early childhood and general pesticide exposure during maternal preconception/pregnancy) were convincingly associated with childhood ALL. Other risk factors including extremely low frequency electromagnetic field (ELF-MF), living in proximity to nuclear facilities, petroleum, benzene, solvent, and domestic paint exposure during early childhood, all showed some level of evidence of association. Maternal consumption of coffee (high consumption/>2 cups/day) and cola (high consumption) during pregnancy, paternal smoking during the pregnancy of the index child, maternal intake of fertility treatment, high birth weight (≥4000 g) and caesarean delivery were also found to have some level of evidence of association. Maternal folic acid and vitamins intake, breastfeeding (≥6 months) and day-care attendance, were inversely associated with childhood ALL with some evidence. The results of this umbrella review should be interpreted with caution; as the evidence stems almost exclusively from case-control studies, where selection and recall bias are potential concerns, and whether the empirically observed association reflect causal relationships remains an open question. Hence, improved exposure assessment methods including accurate and reliable measurement, probing questions and better interview techniques are required to establish causative risk factors of childhood leukemia, which is needed for the ultimate goal of primary prevention.
Context
A negative association between a history of allergy and childhood acute lymphoblastic leukemia (ALL) has been reported in previous studies, but remains debated. This work aimed to investigate this association accounting for genetic polymorphisms of the Th2 pathway cytokines (IL4, IL10, IL13, and IL4R).
Methods
Analyses were based on the French case-control study ESTELLE (2010-2011). The complete sample included 629 ALL cases and 1421 population-based controls frequency-matched on age and gender. The child's medical history was collected through standardized maternal interview. Biological samples were collected, and genotyping data were available for 411 cases and 704 controls of European origin. Odds ratios (OR) were estimated using unconditional regression models adjusted for potential confounders.
Results
In the complete sample, a significant inverse association was observed between ALL and reported history of allergic rhinitis or sinusitis (OR = 0.65 [0.42-0.98]; P = 0.04), but there was no obvious association with allergies overall. There was an interaction between genetic polymorphisms in IL4 and IL4R (Pinteraction = 0.003), as well as a gene-environment interaction between IL4R-rs1801275 and a reported history of asthma (IOR = 0.23; Pint = 0.008) and eczema (IOR = 0.47; Pint = 0.06). We observed no interaction with the candidate polymorphisms in IL4 and IL13.
Conclusion
These results suggest that the association between allergic symptoms and childhood ALL could be modified by IL4R-rs1801275, and that this variant could also interact with a functional variant in IL4 gene. Although they warrant confirmation, these results could help understand the pathological mechanisms under the reported inverse association between allergy and childhood ALL.
This document presents the ICRP's updated vision on “Areas of Research to Support the System of Radiological Protection”, which have been previously published in 2017. It aims to complement the research priorities promoted by other relevant international organisations, with the specificity of placing them in the perspective of the evolution of the System of Radiological Protection. This document contributes to the process launched by ICRP to review and revise the System of Radiological Protection that will update the 2007 General Recommendations in ICRP Publication 103.
Background
Exposure to high doses of ionizing radiation is known to cause cancer. Exposure during childhood is associated with a greater excess relative risk for leukemia and tumors of the central nervous system (CNS) than exposure in later life. Cancer risks associated with low-dose exposure (<100 mSv) are uncertain. We previously investigated the association between the incidence of childhood cancer and levels of exposure to external background radiation from terrestrial gamma and cosmic rays in Switzerland using data from a nationwide census-based cohort study. Here, we provide an update of that study using an extended follow-up period and an improved exposure model.
Methods
We included all children 0–15 years of age registered in the Swiss national censuses 1990, 2000, and 2010–2015. We identified incident cancer cases during 1990–2016 using probabilistic record linkage with the Swiss Childhood Cancer Registry. Exposure to terrestrial and cosmic radiation at children's place of residence was estimated using geographic exposure models based on aerial spectrometric gamma-ray measurements. We estimated and included the contribution from ¹³⁷Cs deposition after the Chernobyl accident. We created a nested case-control sample and fitted conditional logistic regression models adjusting for sex, year of birth, neighborhood socioeconomic position, and modelled outdoor NO2 concentration. We also estimated the population attributable fraction for childhood cancer due to external background radiation.
Results
We included 3,401,113 children and identified 3,137 incident cases of cancer, including 951 leukemia, 495 lymphoma, and 701 CNS tumor cases. Median follow-up in the cohort was 6.0 years (interquartile range: 4.3–10.1) and median cumulative exposure since birth was 8.2 mSv (range: 0–31.2). Hazard ratios per 1 mSv increase in cumulative dose of external background radiation were 1.04 (95% CI: 1.01–1.06) for all cancers combined, 1.06 (1.01–1.10) for leukemia, 1.03 (0.98–1.08) for lymphoma, and 1.06 (1.01–1.11) for CNS tumors. Adjustment for potential confounders had little effect on the results. Based on these results, the estimated population attributable fraction for leukemia and CNS tumors due to external background radiation was 32% (7–49%) and 34% (5–51%), respectively.
Conclusions
Our results suggest that background ionizing radiation contributes to the risk of leukemia and CNS tumors in children.
The radiosensitivity of haematopoietic stem and progenitor cells (HSPCs) to neutron radiation remains largely underexplored, notwithstanding their potential role as target cells for radiation-induced leukemogenesis. New insights are required for radiation protection purposes, particularly for aviation, space missions, nuclear accidents and even particle therapy. In this study, HSPCs (CD34 ⁺ cells) were isolated from umbilical cord blood and irradiated with ⁶⁰ Co γ-rays (photons) and high energy p(66)/Be(40) neutrons. At 2 hours post-irradiation, a significantly higher number of 1.28 ± 0.12 γ-H2AX foci/cell was observed after 0.5 Gy neutrons compared to 0.84 ± 0.14 foci/cell for photons, but this decreased to similar levels for both radiation qualities after 18 hours. However, a signficant difference in late apoptosis was observed between photon and neutron irradiation at 18 hours, 43.17 ± 6.10 % versus 55.55 ± 4.87 %, respectively. A significant increase in cytogenetic damage was observed after both 0.5 and 1 Gy neutron irradiation compared to photons, while there was no difference in the nuclear division index between both radiation qualities. The results point towards a higher induction of DNA damage after neutron irradiation in HSPCs followed by error-prone DNA repair, which contributes to genomic instability and a higher risk of leukemogenesis.
Background
The role of natural background radiation (NBR) in childhood acute leukemia (AL) remains unclear. Several large record based studies have recently reported heterogeneous results. Differences in exposure assessment timing may explain this heterogeneity.
Objectives
In a previous ecological study we did not observe any association between childhood AL incidence in France and NBR exposure at the time of diagnosis. With the same methodology, the present study focused on NBR exposure at the time of birth. Based on data from the French national registry of childhood cancer, we analyzed all AL together, and lymphoblastic and myeloid AL, separately.
Methods
We included 6,059 childhood AL cases born and diagnosed in mainland France between 1990 and 2009. NBR levels in municipalities of residence at birth were estimated by cokriging models, using NBR measurements and precise geological data. The incidence rate ratio (IRR) per unit variation of exposure was estimated with Poisson regression models, with adjustment for socio-demographic indicators and ultraviolet radiation levels. NBR exposures were considered at the time of birth, and cumulatively from birth to diagnosis. We also estimated a total NBR dose to red-bone marrow (RBM).
Results
There was no evidence for an association between NBR exposure at birth and childhood AL incidence, neither overall (gamma radiation: IRR = 0.99 (0.94,1.05) per 50 nSv/h; radon: IRR = 0.97 (0.91,1.03) per 100 Bq/m³) nor for the main AL types. The conclusions were similar with the cumulative exposures, and the total RBM dose.
Conclusions
The study was based on high quality incidence data, large numbers of AL cases, and validated models of NBR exposure assessment. In all, the results further support the hypothesis that NBR are not associated to childhood AL in France.
B cell acute lymphoblastic leukaemia (B-ALL) is the most common form of childhood cancer. Although treatment has advanced remarkably in the past 50 years, it still fails in ~20% of patients. Recent studies revealed that more than 5% of healthy newborns carry preleukaemic clones that originate in utero, but only a small percentage of these carriers will progress to overt B-ALL. The drivers of progression are unclear, but B-ALL incidence seems to be increasing in parallel with the adoption of modern lifestyles. Emerging evidence shows that a major driver for the conversion from the preleukaemic state to the B-ALL state is exposure to immune stressors, such as infection. Here, we discuss our current understanding of the environmental triggers and genetic predispositions that may lead to B-ALL, highlighting lessons from epidemiology, the clinic and animal models, and identifying priority areas for future research.
In this paper, we revisit the possibility, first raised using a data set collected in the 1970s, that there is a link between average radon concentrations and the incidence of childhood leukaemia and lymphoma in Canada. Following the launch of the National Radon Program in 2007, Health Canada completed a long-term radon survey in 33 census metropolitan areas (CMAs), which covers about 70% of the Canadian population. We used this data, together with leukaemia and lymphoma incidence rates among children (0-14 years of age) in the past decade (2006-15), and tried to link the city-level average radon concentrations to the leukaemia and lymphoma incidence rates in 33 major Canadian cities. Analyses were conducted for six subtypes (ALL, AML, CMD, HL, NHL and BL) of leukaemia and lymphoma. Estimated doses to red bone marrow from domestic radon exposure were low and we did not find any association between radon exposure at home and the increased risk for developing leukaemia among children under 15 years of age living in the CMAs. The results indicate a slight positive association for AML among 1-4 year males in CMAs of Peer Group C and NHL among 5-9 year females in CMAs of Peer Group A; however, these should be interpreted with caution owing to the crude exposure assessment and possibilities of other confounding factors.
Key content
The appropriate use of imaging in pregnancy is necessary for prompt investigation and management of acute and chronic medical symptoms.
Healthcare professionals should consider carefully which imaging modality and scanned area of interest will yield maximum diagnostic information.
The use of shielding techniques significantly reduces the dose of ionising radiation to which the fetus is exposed.
Theoretical concerns regarding magnetic resonance imaging use in pregnancy have not been supported in human studies.
Gadolinium contrast should be avoided in pregnancy unless the maternal benefits outweigh fetal and neonatal risks.
Learning objectives
To review the safety of different imaging modalities in pregnancy.
To understand the risks and benefits of various imaging techniques in pregnancy.
To review the investigations required to image common medical symptoms encountered by obstetricians.
Ethical issues
Do obstetricians adequately counsel women regarding safety of imaging in pregnancy to enable them to give informed consent for the procedure?
Increased incidences of childhood acute leukaemia were noted among survivors of the atomic bombings of Hiroshima and Nagasaki. In Western societies, Childhood Acute Lymphoblastic Leukaemia has a distinct epidemiology peaking at 3 years old. Exposure to ionising radiation is an established hazard but it is difficult to gauge the precise risk of less than 100 mSv. Since 1983 significant leukaemia incidences have been reported among families residing near nuclear installations. The target cells (naïve neonatal lymphocytes) get exposed to multiple xenobiotic challenges and undergo extraordinary proliferation and physiological somatic genetic change. Population movements and ionising radiation are considered taking account of updated understanding of radiation biology, cancer cytogenetics and immunological diversity. Double Strand Breaks in DNA arise through metabolic generation of Reactive Oxygen Species, and nearly always are repaired; but mis-repairs can be oncogenic. Recombinant Activating Gene enzymes in rapidly dividing perinatal pre-B lymphocytes being primed for antibody diversity are targeted to Signal Sequences in the Immunoglobulin genes. off target pseudo-sequences may allow RAG enzymes to create autosomal DSBs which, when mis-repaired, become translocated oncogenes. Immunogens acting by chance at crucial stages may facilitate this. In such circumstances, oncogenic DSBs from ionising radiation are less likely to be significant.
Although medical ionizing radiation (IR) has clear clinical benefits, it is an established carcinogen. Our study estimates the number of new cancer cases in France in 2015 attributable to IR exposure from medical procedures. Exposures from external (X‐rays, CT scans, interventional radiology) and internal (nuclear medicine) sources were considered. We used 2007 national frequencies of diagnostic examinations by sex and age to estimate the lifetime organ dose exposure adjusted for changes in the use of such procedures over time. The Biological Effects of Ionizing Radiation VII risk models were used to estimate the corresponding excess cancer risk, assuming an average latency period of 10 years. Additionally, we used cancer incidence data from the French Cancer Registries Network. Of the 346,000 estimated new cancer cases in adults in France in 2015, 2300 cases (940 among men and 1360 among women) were attributable to diagnostic IR, representing 0.7% of all new cancer cases (0.5% for men and 0.9% for women). The leading cancers attributable to medical IR were female breast (n = 560 cases), lung (n = 500 cases) and colon (n = 290 cases) cancers. Compared to other risk factors, the contribution of medical IR to the cancer burden is small, and the benefits largely outweigh its harms. However, some of these IR‐associated cancer cases may be preventable through dose optimization of and enhanced justification for diagnostic examinations.
To evaluate the risk of acute childhood leukaemia in areas of Sweden contaminated after the Chernobyl reactor accident in April 1986.
Population based study of childhood leukaemia diagnosed during 1980-92.
Coordinates for places of residence of all 1.6 million children aged 0-15 years; aerial mapped areas of Sweden heavily contaminated after the Chernobyl accident.
888 children aged 0-15 years with acute leukaemia diagnosed in Sweden during 1980-92, identified with place of birth and residence at diagnosis.
Risk of leukaemia in areas contaminated after the Chernobyl accident compared with the rest of Sweden and in the same areas before the accident.
During six and a half years of follow up after the accident the odds ratio for acute leukaemia was 0.9 (95% confidence interval 0.6 to 1.4) in highly contaminated areas (> or = 10 kBq/m2) compared with the same areas before the accident. For the subgroup acute lymphoblastic leukaemia in children aged under 5 years at diagnosis the odds ratio was 1.5 (0.8 to 2.6). For all cases diagnosed after May 1986 in highly contaminated areas compared with areas of low contamination the odds ratio was 0.9 (0.7 to 1.3). For acute lymphoblastic leukaemia in children aged under 5 years at diagnosis the odds ratio was 1.2 (0.8 to 1.9) in highly contaminated areas compared with areas of low contamination. Dose-response analysis showed no correlation between the degree of contamination and the incidence of childhood leukaemia.
There has been no significant increase in the incidence of acute childhood leukaemia in areas of Sweden contaminated after the Chernobyl reactor accident.
Purpose: Many epidemiological studies have attempted to detect associations between exposure to natural background radiation and childhood cancer. If such a link could be established it would provide evidence that radiation risks continue into a region of low doses and dose rates. However, nearly all previous studies have suffered from insufficient power and/or other design deficiencies. The aim of this work is to test the association between childhood cancer and natural background radiation in a record-based case-control study. This study design offers two important advantages: freedom from participation bias and the potential for much larger studies than those which depend on individual interviews.
Methods: Cases of childhood cancer in children born and diagnosed in Great Britain during 1980–2006 were taken from the UK’s National Registry of Childhood Tumours (NRCT). The NRCT also has controls for each case, matched using birth registers. Radiation exposures were estimated for mother’s residence at the child’s birth. For natural gamma rays, County-District means based on a National Survey were used. Analagous County District means were available for radon but more precise estimates were derived from a predictive map based on domestic measurements grouped by geological boundaries.
Results: A total of 27,447 cancer cases and 36,793 controls were included in the study population. Gamma ray exposures (including the directly ionising component of cosmic rays) were close to 95 nGy per hour. The mean radon exposure was about 22 Bqm3.
Conclusion: Very much larger populations can be studied in such a record-based case-control study than in conventional interview based studies. Power calculations indicate that a study of this size has a power of ~50% to detect an association between gamma rays and childhood leukaemia.
The high doses of alpha-particle radiation which Thorotrast delivers to the testes makes the study of offspring of patients, who were administered this diagnostic contrast medium, particularly relevant to the controversy regarding childhood leukaemia in the offspring of the male Sellafield workforce, as it has been suggested that the alpha-particle dose from actinides may, in part, account for the observed association between paternal pre-conception external irradiation and leukaemia. The risks of childhood leukaemia and non-Hodgkin's lymphoma found among the offspring of the male Danish cohort of neurosurgical patients injected with Thorotrast for cerebral arteriography are compared with those observed in the offspring of the Sellafield (western Cumbria), Ontario and Scottish radiation workers and in the offspring of the Japanese atomic bomb survivors. Risks are compared using linear and exponential forms of a relative risk model. The pre-conception exposure risks of leukaemia, or of leukaemia and non-Hodgkin's lymphoma, in the Danish study are statistically incompatible with the corresponding risks in the children of the Sellafield workforce ( P < 0.01), which is entirely due to incompatibility with the risks in the children of the Sellafield workforce born in Seascale ( P < 0.01). Indeed no cases arose in the Danish study. The statistical incompatibility between the offspring of the Danish patients and the Seascale-born offspring of the Sellafield workforce is independent of the models used and is insensitive to uncertainties in the gonadal dose estimates in the respective datasets or to uncertainties in the estimates of the background cancer rates in the Seascale and Danish populations. The risks of leukaemia and non-Hodgkin's lymphoma in the Danish dataset are statistically compatible with the risks observed in the offspring of the Sellafield workforce born elsewhere in western Cumbria and with those seen among the offspring of the Ontario or Scottish radiation workforces as well as with those in the offspring of the Japanese atomic bomb survivors. The statistical compatibilities of the leukaemia pre-conception exposure risks in these various groups are also independent of the models used. It is most unlikely that the Seascale childhood leukaemia cases are caused by paternal exposures to alpha-particle emitters such as plutonium. In each non-Seascale dataset the risks are consistent with there being no excess hazard of leukaemia associated with paternal pre-conception exposure to ionising radiation, and it would seem that the association seen for Seascale-born children should be attributed to chance.
The European Childhood Leukaemia - Lymphoma Incidence Study (ECLIS) is designed to address concerns about a possible increase in the risk of cancer in Europe following the nuclear accident in Chernobyle in 1986. This paper reports results of surveillance of childhood leukaemia in cancer registry populations from 1980 up to the end of 1991. There was a slight increase in the incidence of childhood leukaemia in Europe during this period, but the overall geographical pattern of change bears no relation to estimated exposure to radiation resulting from the accident. We conclude that at this stage of follow-up any changes in incidence consequent upon the Chernobyl accident remain undetectable against the usual background rates. Our results are consistent with current estimates of the leukaemogenic risk of radiation exposure, which, outside the immediate vicinity of the accident, was small.
Preface:
In July 2001, the then Environment Minister, Michael Meacher MP, announced the establishment of a group with the remit “to consider present risk models for radiation and health that apply to exposure to radiation from internal radionuclides in the light of recent studies and to identify any further research that may be needed”. The Committee thus formed, commenced its work in December 2001 and has held 16 meetings, during which it examined evidence from radiobiology and epidemiology. In June 2003, the Committee prepared a Preliminary Report that was considered by a Workshop of invited delegates in Oxford in July 2003. This final Report has been published and sent to the Committee on Medical Aspects of Radiation in the Environment (COMARE) for its consideration. It is expected that COMARE will wish to inform Ministers of its views on the Report.
We conducted a large record-based case-control study testing associations between childhood cancer and natural background radiation. Cases (27,447) born and diagnosed in Great Britain during 1980-2006 and matched cancer-free controls (36,793) were from the National Registry of Childhood Tumours. Radiation exposures were estimated for mother's residence at the child's birth from national databases, using the County District mean for gamma rays, and a predictive map based on domestic measurements grouped by geological boundaries for radon. There was 12% excess relative risk (ERR) (95% CI 3, 22; two-sided P=0.01) of childhood leukaemia per millisievert of cumulative red bone marrow dose from gamma radiation; the analogous association for radon was not significant, ERR 3% (95% CI -4, 11; P=0.35). Associations for other childhood cancers were not significant for either exposure. Excess risk was insensitive to adjustment for measures of socio-economic status. The statistically significant leukaemia risk reported in this reasonably powered study (power ~50%) is consistent with high-dose rate predictions. Substantial bias is unlikely, and we cannot identify mechanisms by which confounding might plausibly account for the association, which we regard as likely to be causal. The study supports the extrapolation of high-dose rate risk models to protracted exposures at natural background exposure levels.
Little is known about long-term cancer risks following in utero radiation exposure. We evaluated the association between in utero radiation exposure and risk of solid cancer and leukemia mortality among 8,000 offspring, born from 1948-1988, of female workers at the Mayak Nuclear Facility in Ozyorsk, Russia. Mother's cumulative gamma radiation uterine dose during pregnancy served as a surrogate for fetal dose. We used Poisson regression methods to estimate relative risks (RRs) and 95% confidence intervals (CIs) of solid cancer and leukemia mortality associated with in utero radiation exposure and to quantify excess relative risks (ERRs) as a function of dose. Using currently available dosimetry information, 3,226 (40%) offspring were exposed in utero (mean dose = 54.5 mGy). Based on 75 deaths from solid cancers (28 exposed) and 12 (6 exposed) deaths from leukemia, in utero exposure status was not significantly associated with solid cancer: RR = 0.94, 95% CI 0.58 to 1.49; ERR/Gy = -0.1 (95% CI < -0.1 to 4.1), or leukemia mortality; RR = 1.65, 95% CI 0.52 to 5.27; ERR/Gy = -0.8 (95% CI < -0.8 to 46.9). These initial results provide no evidence that low-dose gamma in utero radiation exposure increases solid cancer or leukemia mortality risk, but the data are not inconsistent with such an increase. As the offspring cohort is relatively young, subsequent analyses based on larger case numbers are expected to provide more precise estimates of adult cancer mortality risk following in utero exposure to ionizing radiation.
More accurate reconstruction of the radioactive contamination of the Techa River system in 1949-1951 has been made on the basis of refined data on the amounts and the rate of discharge of radionuclides into the Techa River from the Mayak Production Association; this has led to the development of a modified Techa River model that describes the transport of radionuclides through the up-river ponds and along the Techa River and deposition of radionuclides in the river-bottom sediments and flooded areas. The refined Techa River source-term data define more precisely the time-dependent rates of release and radionuclide composition of the releases that occurred during 1949-1951. The Techa River model takes into account the time-dependent characteristics of the releases and considers (a) the transport of radionuclides adsorbed on solid particles originally contained in the discharges or originating in the up-river ponds as a result of stirring up of contaminated bottom sediments and (b) the transport of radionuclides in soluble form. The output of the Techa River model provides concentrations of all source-term radionuclides in the river water, bottom sediments, and floodplain soils at different distances from the site of radioactive releases for the period of major contamination in 1950-1951. The outputs of the model show good agreement with historical measurements of water and sediment contamination. In addition, the river-model output for (90)Sr concentration in the river water is harmonized with retrospective estimates derived from the measurements of (90)Sr in the residents of the Techa Riverside villages. Modeled contamination of the floodplain soils by (137)Cs is shown to be in agreement with the values reconstructed from late measurements of this radionuclide. Reconstructed estimates of the Techa River contamination are being used for the quantification of internal and external doses received by residents of the Techa Riverside communities.
Although CT scans are very useful clinically, potential cancer risks exist from associated ionising radiation, in particular for children who are more radiosensitive than adults. We aimed to assess the excess risk of leukaemia and brain tumours after CT scans in a cohort of children and young adults.
In our retrospective cohort study, we included patients without previous cancer diagnoses who were first examined with CT in National Health Service (NHS) centres in England, Wales, or Scotland (Great Britain) between 1985 and 2002, when they were younger than 22 years of age. We obtained data for cancer incidence, mortality, and loss to follow-up from the NHS Central Registry from Jan 1, 1985, to Dec 31, 2008. We estimated absorbed brain and red bone marrow doses per CT scan in mGy and assessed excess incidence of leukaemia and brain tumours cancer with Poisson relative risk models. To avoid inclusion of CT scans related to cancer diagnosis, follow-up for leukaemia began 2 years after the first CT and for brain tumours 5 years after the first CT.
During follow-up, 74 of 178,604 patients were diagnosed with leukaemia and 135 of 176,587 patients were diagnosed with brain tumours. We noted a positive association between radiation dose from CT scans and leukaemia (excess relative risk [ERR] per mGy 0·036, 95% CI 0·005-0·120; p=0·0097) and brain tumours (0·023, 0·010-0·049; p<0·0001). Compared with patients who received a dose of less than 5 mGy, the relative risk of leukaemia for patients who received a cumulative dose of at least 30 mGy (mean dose 51·13 mGy) was 3·18 (95% CI 1·46-6·94) and the relative risk of brain cancer for patients who received a cumulative dose of 50-74 mGy (mean dose 60·42 mGy) was 2·82 (1·33-6·03).
Use of CT scans in children to deliver cumulative doses of about 50 mGy might almost triple the risk of leukaemia and doses of about 60 mGy might triple the risk of brain cancer. Because these cancers are relatively rare, the cumulative absolute risks are small: in the 10 years after the first scan for patients younger than 10 years, one excess case of leukaemia and one excess case of brain tumour per 10,000 head CT scans is estimated to occur. Nevertheless, although clinical benefits should outweigh the small absolute risks, radiation doses from CT scans ought to be kept as low as possible and alternative procedures, which do not involve ionising radiation, should be considered if appropriate.
US National Cancer Institute and UK Department of Health.
Second malignant neoplasms (SMNs) and cardiovascular disease (CVD) are among the most serious and life-threatening late adverse effects experienced by the growing number of cancer survivors worldwide and are due in part to radiotherapy. The National Council on Radiation Protection and Measurements (NCRP) convened an expert scientific committee to critically and comprehensively review associations between radiotherapy and SMNs and CVD, taking into account radiobiology; genomics; treatment (ie, radiotherapy with or without chemotherapy and other therapies); type of radiation; and quantitative considerations (ie, dose-response relationships). Major conclusions of the NCRP include: 1) the relevance of older technologies for current risk assessment when organ-specific absorbed dose and the appropriate relative biological effectiveness are taken into account and 2) the identification of critical research needs with regard to newer radiation modalities, dose-response relationships, and genetic susceptibility. Recommendation for research priorities and infrastructural requirements include 1) long-term large-scale follow-up of extant cancer survivors and prospectively treated patients to characterize risks of SMNs and CVD in terms of radiation dose and type; 2) biological sample collection to integrate epidemiological studies with molecular and genetic evaluations; 3) investigation of interactions between radiotherapy and other potential confounding factors, such as age, sex, race, tobacco and alcohol use, dietary intake, energy balance, and other cofactors, as well as genetic susceptibility; 4) focusing on adolescent and young adult cancer survivors, given the sparse research in this population; and 5) construction of comprehensive risk prediction models for SMNs and CVD to permit the development of follow-up guidelines and prevention and intervention strategies.
This is the 14th report in a series of periodic general reports on mortality in the Life Span Study (LSS) cohort of atomic bomb survivors followed by the Radiation Effects Research Foundation to investigate the late health effects of the radiation from the atomic bombs. During the period 1950-2003, 58% of the 86,611 LSS cohort members with DS02 dose estimates have died. The 6 years of additional follow-up since the previous report provide substantially more information at longer periods after radiation exposure (17% more cancer deaths), especially among those under age 10 at exposure (58% more deaths). Poisson regression methods were used to investigate the magnitude of the radiation-associated risks, the shape of the dose response, and effect modification by gender, age at exposure, and attained age. The risk of all causes of death was positively associated with radiation dose. Importantly, for solid cancers the additive radiation risk (i.e., excess cancer cases per 10(4) person-years per Gy) continues to increase throughout life with a linear dose-response relationship. The sex-averaged excess relative risk per Gy was 0.42 [95% confidence interval (CI): 0.32, 0.53] for all solid cancer at age 70 years after exposure at age 30 based on a linear model. The risk increased by about 29% per decade decrease in age at exposure (95% CI: 17%, 41%). The estimated lowest dose range with a significant ERR for all solid cancer was 0 to 0.20 Gy, and a formal dose-threshold analysis indicated no threshold; i.e., zero dose was the best estimate of the threshold. The risk of cancer mortality increased significantly for most major sites, including stomach, lung, liver, colon, breast, gallbladder, esophagus, bladder and ovary, whereas rectum, pancreas, uterus, prostate and kidney parenchyma did not have significantly increased risks. An increased risk of non-neoplastic diseases including the circulatory, respiratory and digestive systems was observed, but whether these are causal relationships requires further investigation. There was no evidence of a radiation effect for infectious or external causes of death.
Epidemiologic studies show that high temperatures are related to mortality, but little is known about the exposure-response function and the lagged effect of heat. We report the associations between daily maximum apparent temperature and daily deaths during the warm season in 15 European cities.
The city-specific analyses were based on generalized estimating equations and the city-specific results were combined in a Bayesian random effects meta-analysis. We specified distributed lag models in studying the delayed effect of exposure. Time-varying coefficient models were used to check the assumption of a constant heat effect over the warm season.
The city-specific exposure-response functions have a V shape, with a change-point that varied among cities. The meta-analytic estimate of the threshold was 29.4 degrees C for Mediterranean cities and 23.3 degrees C for north-continental cities. The estimated overall change in all natural mortality associated with a 1 degrees C increase in maximum apparent temperature above the city-specific threshold was 3.12% (95% credibility interval = 0.60% to 5.72%) in the Mediterranean region and 1.84% (0.06% to 3.64%) in the north-continental region. Stronger associations were found between heat and mortality from respiratory diseases, and with mortality in the elderly.
There is an important mortality effect of heat across Europe. The effect is evident from June through August; it is limited to the first week following temperature excess, with evidence of mortality displacement. There is some suggestion of a higher effect of early season exposures. Acclimatization and individual susceptibility need further investigation as possible explanations for the observed heterogeneity among cities.
Natural sources contribute a large fraction of the radiation exposure of the general public. Under the linear no-threshold hypothesis risk decreases in proportion to decreasing dose without a threshold. We use recent estimates of doses to the red bone marrow to calculate the number and proportion of cases of leukemia in England induced by natural radiation. We calculate that about 5% of cases of leukemia, excluding chronic lymphocytic leukemia, up to the age of 80 years are induced by this background radiation. In young people up to the age of 25 years the attributable fraction is about 15%, substantially lower than a previous estimate.
To examine childhood cancer risks associated with exposure to diagnostic radiation and ultrasound scans in utero and in early infancy (age 0-100 days).
Case-control study.
England and Wales.
2690 childhood cancer cases and 4858 age, sex, and region matched controls from the United Kingdom Childhood Cancer Study (UKCCS), born 1976-96.
Risk of all childhood cancer, leukaemia, lymphoma, and central nervous system tumours, measured by odds ratios.
Logistic regression models conditioned on matching factors, with adjustment for maternal age and child's birth weight, showed no evidence of increased risk of childhood cancer with in utero exposure to ultrasound scans. Some indication existed of a slight increase in risk after in utero exposure to x rays for all cancers (odds ratio 1.l4, 95% confidence interval 0.90 to 1.45) and leukaemia (1.36, 0.91 to 2.02), but this was not statistically significant. Exposure to diagnostic x rays in early infancy (0-100 days) was associated with small, non-significant excess risks for all cancers and leukaemia, as well as increased risk of lymphoma (odds ratio 5.14, 1.27 to 20.78) on the basis of small numbers.
Although the results for lymphoma need to be replicated, all of the findings indicate possible risks of cancer from radiation at doses lower than those associated with commonly used procedures such as computed tomography scans, suggesting the need for cautious use of diagnostic radiation imaging procedures to the abdomen/pelvis of the mother during pregnancy and in children at very young ages.
Some relatively new issues that augment the usual practice of ignoring model uncertainty, when making inference about parameters of a specific model, are brought to the attention of the radiation protection community here. Nine recently published leukaemia risk models, developed with the Japanese A-bomb epidemiological mortality data, have been included in a model-averaging procedure so that the main conclusions do not depend on just one type of model or statistical test. The models have been centred here at various adult and young ages at exposure, for some short times since exposure, in order to obtain specially computed childhood Excess Relative Risks (ERR) with uncertainties that account for correlations in the fitted parameters associated with the ERR dose-response. The model-averaged ERR at 1 Sv was not found to be statistically significant for attained ages of 7 and 12 years but was statistically significant for attained ages of 17, 22 and 55 years. Consequently, such risks when applied to other situations, such as children in the vicinity of nuclear installations or in estimates of the proportion of childhood leukaemia incidence attributable to background radiation (i.e. low doses for young ages and short times since exposure), are only of very limited value, with uncertainty ranges that include zero risk. For example, assuming a total radiation dose to a 5-year-old child of 10 mSv and applying the model-averaged risk at 10 mSv for a 7-year-old exposed at 2 years of age would result in an ERR=0.33, 95% CI: -0.51 to 1.22. One model (United Nations scientific committee on the effects of atomic radiation report. Volume 1. Annex A: epidemiological studies of radiation and cancer, United Nations, New York, 2006) weighted model-averaged risks of leukaemia most strongly by half of the total unity weighting and is recommended for application in future leukaemia risk assessments that continue to ignore model uncertainty. However, on the basis of the analysis presented here, it is generally recommended to take model uncertainty into account in future risk analyses.
The association between fetal exposure to major radiodiagnostic testing in pregnancy-computed tomography (CT) and radionuclide imaging-and the risk of childhood cancer is not established.
We completed a population-based study of 1.8 million maternal-child pairs in the province of Ontario, from 1991 to 2008. We used Ontario's universal health care-linked administrative databases to identify all term obstetrical deliveries and newborn records, inpatient and outpatient major radiodiagnostic services, as well as all children with a malignancy after birth. There were 5,590 mothers exposed to major radiodiagnostic testing in pregnancy (3.0 per 1,000) and 1,829,927 mothers not exposed. The rate of radiodiagnostic testing increased from 1.1 to 6.3 per 1,000 pregnancies over the study period; about 73% of tests were CT scans. After a median duration of follow-up of 8.9 years, four childhood cancers arose in the exposed group (1.13 per 10,000 person-years) and 2,539 cancers in the unexposed group (1.56 per 10,000 person-years), a crude hazard ratio of 0.69 (95% confidence interval 0.26-1.82). After adjusting for maternal age, income quintile, urban status, and maternal cancer, as well as infant sex, chromosomal or congenital anomalies, and major radiodiagnostic test exposure after birth, the risk was essentially unchanged (hazard ratio 0.68, 95% confidence interval 0.25-1.80).
Although major radiodiagnostic testing is now performed in about 1 in 160 pregnancies in Ontario, the absolute annual risk of childhood malignancy following exposure in utero remains about 1 in 10,000. Since the upper confidence limit of the relative risk of malignancy may be as high as 1.8 times that of an unexposed pregnancy, we cannot exclude the possibility that fetal exposure to CT or radionuclide imaging is carcinogenic.
The etiology of childhood leukemia remains generally unknown, although risk models based on the Japanese A-bomb survivors imply that the dose accumulated from protracted exposure to low-level natural background ionizing radiation materially raises the risk of leukemia in children. In this paper a novel Monte Carlo score-test methodology is used to assess the statistical power of cohort, ecological and case-control study designs, using the linear low-dose part of the BEIR V model derived from the Japanese data. With 10 (or 20) years of follow-up of childhood leukemias in Great Britain, giving about 4600 (or 9200) cases, under an individual-based cohort design there is 67.9% (or 90.9%) chance of detecting an excess (at 5% significance level, one-sided test); little difference is made by extreme heterogeneity in risk. For an ecological design these figures reduce to 57.9% (or 83.2%). Case-control studies with five controls per case achieve much of the power of a cohort design, 61.1% (or 86.0%). However, participation bias may seriously affect studies that require individual consent, and area-based studies are subject to severe interpretational problems. For this reason register-based studies, in particular those that make use of predicted doses that avoid the need for interviews, have considerable advantages. We argue that previous studies have been underpowered (all have power <80%), and some are also subject to unquantifiable biases and confounding. Sufficiently large studies should be capable of detecting the predicted risk attributable to natural background radiation.
Notably raised rates of childhood leukaemia incidence have been found near some nuclear installations, in particular Sellafield and Dounreay in the United Kingdom, but risk assessments have concluded that the radiation doses estimated to have been received by children or in utero as a result of operations at these installations are much too small to account for the reported increases in incidence. This has led to speculation that the risk of childhood leukaemia arising from internal exposure to radiation following the intake of radioactive material released from nuclear facilities has been substantially underestimated. The radionuclides discharged from many nuclear installations are similar to those released into the global environment by atmospheric nuclear weapons testing, which was at its height in the late-1950s and early-1960s. Measurements of anthropogenic radionuclides in members of the general public resident in the vicinity of Sellafield and Dounreay have found levels that do not differ greatly from those in persons living remote from nuclear installations that are due to ubiquitous exposure to the radioactive debris of nuclear weapons testing. Therefore, if the leukaemia risk to children resulting from deposition within the body of radioactive material discharged from nuclear facilities has been grossly underestimated, then a pronounced excess of childhood leukaemia would have been expected as a consequence of the short period of intense atmospheric weapons testing. We have examined childhood leukaemia incidence in 11 large-scale cancer registries in three continents for which data were available at least as early as 1962. We found no evidence of a wave of excess cases corresponding to the peak of radioactive fallout from atmospheric weapons testing. The absence of a discernible increase in the incidence of childhood leukaemia following the period of maximum exposure to the radioactive debris of this testing weighs heavily against the suggestion that conventional methods are seriously in error when assessing the risk of childhood leukaemia from exposure to man-made radionuclides released from nuclear installations.
Beginning in 1950, people living on the banks of the Techa River received chronic low-dose-rate internal and external radiation exposures as a result of releases from the Mayak nuclear weapons plutonium production facility in the Southern Urals region of the Russian Federation. The Techa River cohort includes about 30,000 people who resided in riverside villages sometime between 1950 and 1960. Cumulative red bone marrow doses range up to 2 Gy with a mean of 0.3 Gy and a median of 0.2 Gy. Between 1953 and 2005, 93 first primary cases of leukemia, including 23 cases of chronic lymphatic leukemia (CLL), were ascertained among the cohort members. A significant linear dose-response relationship was seen for leukemias other than CLL (P < 0.001), but not for CLL. The estimated excess relative risk per Gy is 4.9 (95% confidence interval (CI): 1.6; 14.3) for leukemias other than CLL and less than 0 (95% upper bound 1.4) for CLL.
The aetiology of childhood leukaemia remains generally unknown, although exposure to moderate and high levels of ionising radiation, such as was experienced during the atomic bombings of Japan or from radiotherapy, is an established cause. Risk models based primarily upon studies of the Japanese A-bomb survivors imply that low-level exposure to ionising radiation, including to ubiquitous natural background radiation, also raises the risk of childhood leukaemia. In a recent paper (Wakeford et al 2009 Leukaemia 23 770-6) we estimated the proportion of childhood leukaemia incidence in Great Britain attributable to natural background radiation to be about 20%. In this paper we employ the two sets of published leukaemia risk models used previously, but use recently published revised estimates of natural background radiation doses received by the red bone marrow of British children to update the previous results. Using the newer dosimetry we calculate that the best estimate of the proportion of cases of childhood leukaemia in Great Britain predicted to be attributable to this source of exposure is 15-20%, although the uncertainty associated with certain stages in the calculation (e.g. the nature of the transfer of risk between populations and the pertinent dose received from naturally occurring alpha-particle-emitting radionuclides) is significant. The slightly lower attributable proportions compared with those previously derived by Wakeford et al (Leukaemia 2009 23 770-6) are largely due to the lower doses (and in particular lower high LET doses) for the first year of life.
Ionizing radiation is an established cause of cancer, yet little is known about the health effects of doses from diagnostic examinations in children. The risk of childhood cancer was studied in a cohort of 92.957 children who had been examined with diagnostic X rays in a large German hospital during 1976-2003. Radiation doses were reconstructed using the individual dose area product and other exposure parameters, together with conversion coefficients developed specifically for the medical devices and standards used at the radiology department. Newly diagnosed cancers occurring between 1980 and 2006 were determined through record linkage to the German Childhood Cancer Registry. The median radiation dose was 7 microSv. Eight-seven incident cases were found in the cohort: 33 leukemia, 13 lymphoma, 10 central nervous system tumors, and 31 other tumors. The standardized incidence ratio (SIR) for all cancers was 0.99 (95% CI: 0.79-1.22). No trend in the incidence of total cancer, leukemia or solid tumors with increasing radiation dose was observed in the SIR analysis or in the multivariate Poisson regression. Risk did not differ significantly in girls and boys. Overall, while no increase in cancer risk with diagnostic radiation was observed, the results are compatible with a broad range of risk estimates.
The aetiology of childhood leukaemia remains generally unknown, although exposure to moderate and high levels of ionizing radiation, such as those experienced during the atomic bombings of Japan or from radiotherapy, is an established cause. Risk models based primarily on studies of the Japanese atomic bomb survivors imply that low-level exposure to ionizing radiation, including ubiquitous natural background radiation, also raises the risk of childhood leukaemia. Using two sets of recently published leukaemia risk models and estimates of natural background radiation red-bone-marrow doses received by children, about 20% of the cases of childhood leukaemia in Great Britain are predicted to be attributable to this source. However, for one of these sets of risk models this attributable fraction is materially dependent on how the radiation-induced risk is assumed to be transferred between the Japanese atomic bomb survivors and Western children. Over a range of annual doses representing the range (0.5-2.5 mSv/year) experienced by most populations, the attributable proportion for the preferred risk-transfer model varies between 8 and 30%, with small deviations from a linear relationship that are largely due to the saturation of the model, although again this range of attributable fractions depends on the assumed transfer of risk between populations.
Since the reports in 1956 and 1958 that in utero radiation was associated with an increased risk of leukemia and solid cancers during childhood, this issue has been debated. Many epidemiological studies have been performed. Evidence for a causal association derives almost entirely from case‐control studies, whereas practically all cohort studies find no association, most notably the series of atomic bomb survivors exposed in utero. Although it is likely that in utero radiation presents a leukemogenic risk to the fetus, the magnitude of the risk remains uncertain. The causal nature of the risk of cancers other than leukemia is less convincing, and the similar relative risks (RR = 1.5) for virtually all forms of childhood cancer suggests an underlying bias. Few studies have addressed the potential risk of adult cancer after intrauterine exposure. Radiotherapy given to newborns, however, has been linked to cancers of the thyroid and breast later in life. Teratology 59:227–233, 1999. © 1999 Wiley‐Liss, Inc.
Demographic information and radiation factors are presented for 2,809 children treated with X rays for thymic enlargement in an upstate New York county between 1926 and 1957. Approximately half the children had been studied previously. The remainder were new cases. Information regarding the health and mortality of the treated children of both series was collected by mail survey in 1959–60. Procedures for tracing families and other methodological aspects of the survey, including the design of the questionnaire and response rates, are described. Radiation dosage factors used in treatment are believed to be accurate. Almost all the children were irradiated before the age of 6 months. Many of the older children were given relatively high doses of X rays to large areas that often involved the posterior as well as the anterior aspects of the chest. The younger children were usually given lower doses of X rays to relatively small anterior areas. The 1,451 children previously studied had a high incidence of tumors, particularly leukemia and thyroid neoplasms. The present survey shows that these children continued to develop tumors at a higher rate than that of their untreated siblings and higher than that expected in a comparable group from the general population. Thyroid adenomas and carcinomas comprise about one half, and osteochondromas, about one sixth of all tumors. No new cases of leukemia have occurred since the previous survey. Several cases of salivary gland tumors and neurilemmomas, which are very rare neoplasms in children and young adults, were observed. Data on mortality of treated children and their siblings in both series are difficult to evaluate. The moderate excess of deaths in the children of series I after the 1st year of life can be attributed largely to 6 cases of leukemia. Relatively few other deaths have resulted from malignant disease.
Cancer is diagnosed in about 140 per million children in Britain each year. There is a 1 in 500 chance that a child will be affected in the first 15 years of life, the most frequently occurring types of cancer being leukaemia and brain tumours. This book covers the descriptive epidemiology of childhood cancer in Britain through a series of analyses based on data from the National Registry of Childhood Tumours, the largest population-based specialist children's cancer registry in the world. The central four chapters are devoted to detailed analyses of the data. Throughout these chapters, the diagnoses are classified according to the International Classification of Childhood Cancer, Third Edition. First, there is a comprehensive account of national incidence during 1991-2000, with tables of rates and age-incidence graphs for all the major types of childhood cancer. This is followed by an analysis of incidence trends during 1966-2000. The chapter on survival includes a detailed account of survival rates for 1991-2000, analyses of trends during 1966-2000 with a discussion of how they are related to clinical progress, and information on long-term survival. The chapter on mortality gives an account of childhood cancer mortality during 1965-2004. These chapters are preceded by accounts of the history and methodology of the registry, and of the methods used for analyzing the data. The book concludes with a review of past, current and future functions of the registry and uses of its data.
Background Low-dose ionizing radiation is one of the definitive risk factors for cancer development. Nevertheless, only a few follow-up studies of children subjected to cardiac catheterization have been performed, yielding inconsistent results. Methods Our study group included 674 children who underwent cardiac catheterization due to congenital anomalies, between the years 1950-1970 in three major medical centres in Israel. A registered nurse conducted a review of the children's medical files in each hospital. Demographic data and vital status were ascertained from the Israeli National Registry, using a unique identity number. Subsequently, the study cohort was linked with the Israeli National Cancer Registry, in order to identify cancer cases that had been diagnosed through December 1996, the last follow-up date of the study. Results Over 75% of the study participants were native-born; 56.2% were males. Approximately 78% of the cohort subjects were alive at the end of follow-up; 28.6% of the participants underwent more than one procedure. All of the diagnosed cases occurred in males. Expected number of malignancies for all sites was 4.75, while the observed number was 11.0 (standardized incidence ratio [SIR] = 2.3; 95% CI : 1.2-4.1). Of the 11cancer cases, 4 lymphomas were observed (0.63 were expected, SIR = 6.3; 95% CI : 1.7-16.2). One of these was Hodgkin's Disease. There were also three cases of melanoma as opposed to 0.62 expected (SIR = 4.9; 95% CI : 1.0-14.2). Conclusions This finding is compatible with current knowledge about the carcinogenic effect of low-dose irradiation but differs in the occurrence of an excess of lymphoma in the absence of an excess of leukaemia, which has not been reported before. The dissonance between males and females is yet to be resolved. Implications Radiation doses that are used currently during cardiac catheterizatior are lower than in the past. Yet, the procedure is more common and frequently involves longer duration due to therapeutic interventions. The possible long-term results of such an exposure should be kept in mind.
This study compares the illness experience of 2,043 tinea capitis patients during a 12-year period after x-ray epilation with that of 1,413 nonirradiated tinea capitis patients who were also treated during the years 1940 to 1959 at the Skin and Cancer Unit of the New York University Hospital. The irradiated and control groups, surveyed by questionnaire, represented 85% and 79%, respectively, of the total available clinic population of tinea capitis cases and were well matched for age, sex, and race. The major findings of the study included a higher incidence of confirmed cases of cancer and mental illness in the irradiated group.
Increases in the incidence of childhood leukaemia have been reported in the vicinity of several nuclear installations. Conventional models of risk of radiation-induced leukaemia are clearly inconsistent with the assumption that these increases are due to radiation exposure resulting from the proximity of these nuclear installations. Alternative interpretations are that the reported increases are (in some way) an artefact, that the increases are real but are not primarily due to radiation, that the population, or individuals within it, have received higher doses than expected, that present risk models are seriously flawed or that more indirect (e.g. genetic) pathways involving radiation are implicated. Present evidence makes it unlikely that population radiation doses or radiation risk factors could be in error by such large magnitudes as would be required. Attention has therefore focused on indirect mechanisms. Areas where further investigation may prove rewarding include radiation genetics, the chemistry of transuranic elements, personalized dosimetry and models of the role of hypothetical fluctuations in dose delivery, heterogeneity of dose and sensitivity within the population and the interaction of radiation with other agents.
Previous studies reported an association between leukemia rates and amounts of fallout in southwestern Utah from nuclear tests (1952 to 1958), but individual radiation exposures were unavailable. Therefore, a case-control study with 1177 individuals who died of leukemia and 5330 other deaths (controls) was conducted using estimates of dose to bone marrow computed from fallout deposition rates and subjects' residence locations. A weak association between bone marrow dose and all types of leukemia, all ages, and all time periods after exposure was found. This overall trend was not statistically significant, but significant trends in excess risk were found in subgroups defined by cell type, age, and time after exposure. The greatest excess risk was found in those individuals in the high-dose group with acute leukemia who were younger than 20 years at exposure and who died before 1964. These results are consistent with previous studies and with risk estimates for other populations exposed to radiation.
(JAMA. 1990;264:585-591)