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Yuan-Chin Amy Lee,
Daniela Zugna,
Lorenzo Richiardi,
Franco Merletti,
Manuela Marron,
Wolfgang Ahrens,
Hermann Pohlabeln,
Pagona Lagiou,
Dimitrios Trichopoulos,
Antonio Agudo, [......],
Lorenzo Simonato,
David I Conway, Patricia A McKinney,
Peter Thomson,
Ariana Znaor,
Claire M Healy,
Bernard E McCartan,
Paolo Boffetta,
Paul Brennan,
Mia Hashibe
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ABSTRACT: While previous studies on tobacco and alcohol and the risk of upper-aerodigestive-tract (UADT) cancers have clearly shown dose-response relations with the frequency and duration of tobacco and alcohol, studies on addiction to tobacco smoking itself as a risk factor for UADT cancer have not been published, to our knowledge. The aim of this report is to assess whether smoking addiction is an independent risk factor or a refinement to smoking variables (intensity and duration) for UADT squamous cell carcinoma (SCC) risk in the multicenter case-control study (ARCAGE) in Western Europe. The analyses included 1,586 ever smoking UADT SCC cases and 1,260 ever smoking controls. Addiction was measured by a modified Fagerström score (first cigarette after waking up, difficulty refraining from smoking in places where it is forbidden, and cigarettes per day). Adjusted odds ratios (OR) and 95% confidence intervals (95% CI) for UADT cancers with addiction variables were estimated with unconditional logistic regression. Among current smokers, the participants who smoked their first cigarette within 5 minutes of waking up were two times more likely to develop UADT SCC than those who smoked 60 minutes after waking up. Greater tobacco smoking addiction was associated with an increased risk of UADT SCC among current smokers (OR=3.83, 95% CI 2.56-5.73 for score of 3-7 vs. 0), but not among former smokers. These results may be consistent with a residual effect of smoking that was not captured by the questionnaire responses (smoking intensity and smoking duration) alone, suggesting addiction a refinement to smoking variables. © 2013 Wiley Periodicals, Inc.
International Journal of Cancer 05/2013; · 5.44 Impact Factor
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Richard J Q McNally,
Karen Blakey,
Roger C Parslow,
Peter W James,
Basilio Gómez Pozo,
Charles Stiller,
Tim J Vincent,
Paul Norman, Patricia A McKinney,
Michael F Murphy,
Alan W Craft,
Richard G Feltbower
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ABSTRACT: The aetiology of bone cancers is poorly understood. This study examined geographical patterning in incidence of primary bone cancers diagnosed in 0-49 year olds in Great Britain during 1980-2005 to provide information on factors linked with disease development. We investigated putative associations with deprivation and population density.
Data on osteosarcoma and Ewing sarcoma were obtained from national population-based registries. Negative binomial regression was used to examine the relationship between incidence rates and the Townsend deprivation score (and its component variables) and small-area population density.
The study analyzed 2566 osteosarcoma and 1650 Ewing sarcoma cases. For females with osteosarcoma, statistically significant decreased risk was associated with higher levels of deprivation (relative risk [RR] per unit increase in deprivation score = 0.969; 95% confidence interval [CI] 0.946-0.993). For all Ewing sarcoma combined, statistically significant decreased risk was associated with greater area-level population density and higher levels of non-car ownership (RR per person per hectare increase = 0.984; 95% CI 0.976-0.993, RR per 1% increase in non-car ownership = 0.994; 95% CI 0.991-0.998).
Higher incidence of osteosarcoma was observed for females in areas with lower deprivation levels indicating increased risk is linked to some aspect of affluent living. Higher incidence of Ewing sarcoma occurred in areas of low population density and where more people owned cars, both characteristic of rural environments. The study adds substantially to evidence associating Ewing sarcoma risk with rural environmental exposures. Putative risk factors include agricultural exposures, such as pesticides and zoonotic agents.
BMC Cancer 06/2012; 12:270. · 3.01 Impact Factor
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ABSTRACT: Life-limiting conditions (LLCs) describe diseases with no reasonable hope of cure that will ultimately be fatal. For children with these diseases, palliative care services should be available but few data are available to estimate the burden of these conditions.
Children (0-19 years) with LLCs were identified within an English Hospital Episode Statistics dataset (2000/2001-2009/2010) by applying a customized coding framework of the International Classification of Diseases, 10th Revision, disease codes. Prevalence per 10 000 population (0-19 years) was calculated by age, diagnostic group, ethnicity, deprivation, and region for each year.
The Hospital Episode Statistics extract contained 175 286 individuals with 1 or more LLCs of which congenital anomalies were the most common (31%). Prevalence increased over 10 years from 25 to 32 per 10 000 population. Prevalence in the South Asian (48 per 10 000); black (42 per 10 000); and Chinese, mixed, and "other" (31 per 10 000) populations were statistically significantly higher compared with the white population (27 per 10 000). Prevalence shows an inverse J-shaped relationship with 5 categories of deprivation, with the highest prevalence in the most deprived areas and the lowest in the second least deprived.
In 2010, the prevalence of LLCs in children in England was double the previously reported estimates and had increased annually in all areas over the past decade. This clearly identifies an escalating need for specialist pediatric palliative care services. When planning services for these increasing needs, the excess prevalence in ethnic minority groups, especially in deprived areas, needs to be considered.
PEDIATRICS 03/2012; 129(4):e923-9. · 4.47 Impact Factor
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ABSTRACT: We specifically tested the aetiological hypothesis that a factor influencing geographical or temporal heterogeneity of childhood central nervous system (CNS) tumour incidence was related to exposure to a transient environmental agent.
Information was extracted on individuals aged 0-14 years, diagnosed with a CNS tumour between the 1st January 1974 and 31st December 2006 from the Yorkshire Specialist Register of Cancer in Children and Young People. Ordnance Survey eight-digit grid references were allocated to each case with respect to addresses at the time of birth and the time of diagnosis, locating each address to within 0.1 km. The following diagnostic groups were specified a priori for analysis: ependymoma; astrocytoma; primitive neuroectodermal tumours (PNETs); other gliomas; total CNS tumours. We applied the K-function method for testing global space-time clustering using fixed geographical distance thresholds. Tests were repeated using variable nearest neighbour (NN) thresholds.
There was statistically significant global space-time clustering for PNETs only, based on time and place of diagnosis (P = 0.03 and 0.01 using the fixed geographical distance and the variable NN threshold versions of the K-function method respectively).
There was some evidence for a transient environmental component to the aetiology of PNETs. However, a possible role for chance cannot be excluded.
BMC Cancer 01/2012; 12:13. · 3.01 Impact Factor
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ABSTRACT: To determine where children die following discharge from paediatric intensive care units (PICUs) in Great Britain and to investigate if this varies by discharge to palliative care.
National cohort of PICU admissions linked to Office of National Statistics death certificate data.
31 PICUs in Great Britain.
A cohort of 35 383 children admitted to PICUs between 1 November 2002 until 25 January 2007.
Place of death by palliative care discharge status.
2346 (6.6%) deaths occurred after discharge during the study period, which is more than 10 times the normal child population mortality of 6.0 per 1000. Discharge to palliative care resulted in fewer deaths in hospital (44.1%) (compared to non-palliative care discharges (77.7%)), a greater proportion of deaths were at home (33.3% compared to non-palliative discharges 16.1%) and in a hospice (22.5% compared to non-palliative discharges 5.8%).
Children referred to palliative care services at discharge from PICU are more likely to die in the community (home or hospice) than children not referred to palliative care.
Archives of Disease in Childhood 12/2011; 96(12):1195-8. · 2.88 Impact Factor
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ABSTRACT: Background: Progressive neuromuscular disease in children is life limiting and these children and young people would benefit from palliative care services, but data are limited on the number and demography of these children. Aim: To describe the clinical and demographic profile of children referred to a Children's hospice in the UK with progressive neuromuscular disease. Setting/participants: All children and young people with progressive neuromuscular disorders referred to Martin House Children's Hospice between 1987 and 2010. Design: Retrospective cohort study Results: 300 children with progressive neuromuscular disease were referred to the hospice. Seventy percent (210) of these children had Duchenne Muscular Dystrophy, 22% (67) had Spinal Muscular Atrophy (34 with Type I) and 8% had other neuromuscular diseases. Numbers of referrals have not significantly increased over the last 15 years, although an increasing number come from a South Asian background (from 4% to 32%) and a higher number of children have conditions other than Duchenne Muscular Dystrophy. A total of 55.3% (166) of all referrals came from areas of the highest deprivation. Survival patterns varied by diagnostic group, but ethnicity and deprivation were not associated with survival in these children. Conclusions: The profile of children with progressive neuromuscular conditions who were referred for palliative care has changed over the last 20 years, with a different spectrum of underlying diagnoses and a greater number from a South Asian background. The higher than expected proportion of children living in areas of high deprivation has been consistent over time.
Palliative Medicine 09/2011; 26(7):924-9. · 2.38 Impact Factor
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Devasena Anantharaman,
Manuela Marron,
Pagona Lagiou,
Evangelia Samoli,
Wolfgang Ahrens,
Hermann Pohlabeln,
Alena Slamova,
Miriam Schejbalova,
Franco Merletti,
Lorenzo Richiardi, [......],
Cristina Canova,
David I Conway, Patricia A McKinney,
Peter Thomson,
Ariana Znaor,
Claire M Healy,
Bernard E McCartan,
Mia Hashibe,
Paul Brennan,
Gary J Macfarlane
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ABSTRACT: Tobacco and alcohol are major risk factors for upper aerodigestive tract (UADT) cancer and significant variation is observed in UADT cancer rates across Europe. We have estimated the proportion of UADT cancer burden explained by tobacco and alcohol and how this varies with the incidence rates across Europe, cancer sub-site, gender and age. This should help estimate the minimum residual burden of other risk factors to UADT cancer, including human papillomavirus. We analysed 1981 UADT cancer cases and 1993 controls from the ARCAGE multicentre study. We estimated the population attributable risk (PAR) of tobacco alone, alcohol alone and their joint effect. Tobacco and alcohol together explained 73% of UADT cancer burden of which nearly 29% was explained by smoking alone, less than 1% due to alcohol on its own and 44% by the joint effect of tobacco and alcohol. Tobacco and alcohol together explained a larger proportion of hypopharyngeal/laryngeal cancer (PAR=85%) than oropharyngeal (PAR=74%), esophageal (PAR=67%) and oral cancer (PAR=61%). Tobacco and alcohol together explain only about half of the total UADT cancer burden among women. Geographically, tobacco and alcohol explained a larger proportion of UADT cancer in central (PAR=84%) than southern (PAR=72%) and western Europe (PAR=67%). While the majority of the UADT cancers in Europe are due to tobacco or the joint effect of tobacco and alcohol, our results support a significant role for other risk factors in particular, for oral and oropharyngeal cancers and also for UADT cancers in southern and western Europe.
Oral Oncology 06/2011; 47(8):725-31. · 2.86 Impact Factor
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Lorenzo Richiardi,
Marine Corbin,
Manuela Marron,
Wolfgang Ahrens,
Hermann Pohlabeln,
Pagona Lagiou,
Ploumitsa Minaki,
Antonio Agudo,
Xavier Castellsague,
Alena Slamova, [......],
Linda Sneddon,
Peter Thomson,
Ariana Znaor,
Claire M Healy,
Bernard E McCartan,
Simone Benhamou,
Christine Bouchardy,
Mia Hashibe,
Paul Brennan,
Franco Merletti
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ABSTRACT: We investigated the association between occupational history and upper aerodigestive tract (UADT) cancer risk in the ARCAGE European case-control study. The study included 1,851 patients with incident cancer of the oral cavity, oropharynx, hypopharynx, larynx or esophagus and 1,949 controls. We estimated odds ratios (OR) and 95% confidence intervals (CI) for ever employment in 283 occupations and 172 industries, adjusting for smoking and alcohol. Men (1,457 cases) and women (394 cases) were analyzed separately and we incorporated a semi-Bayes adjustment approach for multiple comparisons. Among men, we found increased risks for occupational categories previously reported to be associated with at least one type of UADT cancer, including painters (OR = 1.74, 95% CI: 1.01-3.00), bricklayers (1.58, 1.05-2.37), workers employed in the erection of roofs and frames (2.62, 1.08-6.36), reinforced concreters (3.46, 1.11-10.8), dockers (2.91, 1.05-8.05) and workers employed in the construction of roads (3.03, 1.23-7.46), general construction of buildings (1.44, 1.12-1.85) and cargo handling (2.60, 1.17-5.75). With the exception of the first three categories, risks both increased when restricting to long duration of employment and remained elevated after semi-Bayes adjustment. Increased risks were also found for loggers (3.56, 1.20-10.5) and cattle and dairy farming (3.60, 1.15-11.2). Among women, there was no clear evidence of increased risks of UADT cancer in association with occupations or industrial activities. This study provides evidence of an association between some occupational categories and UADT cancer risk among men. The most consistent findings, also supported by previous studies, were obtained for specific workers employed in the construction industry.
International Journal of Cancer 06/2011; 130(10):2397-406. · 5.44 Impact Factor
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ABSTRACT: High dependency care (HDC) is a level of care situated between intensive care and usual ward care with its delivery being independent of location. Inadequate definition makes it problematic to determine the number of children receiving HDC, to identify their care setting and therefore to undertake service planning. We aimed to estimate the volume of hospital inpatient HDC in a geographically defined population using a customised measurement tool in four types of paediatric hospital services (1) tertiary specialist wards, (2) tertiary paediatric intensive care units, (3) district general hospitals (DGHs) general wards and (4) wards at a major acute general hospital. A region-wide prospective cohort study during 2005 collected data to develop a 36-item HDC measurement tool, which then identified children receiving HDC by day and night. The cohort identified 1,763 children as receiving HDC during an admission to 1 of 36 hospital wards in 14 hospitals. HDC was delivered during 9,077 shift periods of 12 h or 4,538 bed days. The volume of care and patient profiles varied by hospital type, within hospital by ward type and by age and season. Tertiary specialist wards and ICUs provided 72% of HDC, with the remainder delivered at the DGHs and the major acute general hospital. The volume of admissions to tertiary specialist wards showed little seasonality and children tended to be older (26% were aged 10-15 years). By comparison, admissions to DGHs were younger with an excess during the winter months. This is the first UK study to quantify HDC from empirical data encompassing all hospital and ward types within a large clinical network. A lack of HDC-designated beds across the region resulted in HDC delivery on all types of hospital wards. The study size and representativeness makes the estimated number of HDC bed days per head of population likely to reflect the wider UK population.
European Journal of Pediatrics 05/2011; 171(1):77-85. · 1.88 Impact Factor
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ABSTRACT: The availability of resource (staffing and services) in all 21 paediatric diabetes services in Yorkshire and Humber Strategic Health Authority, UK was surveyed and this information was combined with demographic and clinical data on 2683 children and young people with diabetes (aged 0-23 years) to assess whether level of resource was associated with glycaemic control (mean HbA1c %). Multilevel modelling and graphical techniques were used to analyse the relationship between resource and outcome for paediatric diabetes services. No services achieved all resource recommendations based on National Institute for Health and Clinical Excellence guidelines, but there was no direct association between level of resource and glycaemic control after controlling for deprivation, age and duration of diabetes. Transitional care, nurse caseload and access to specialist services are not adequately resourced but variation in outcome between services is not accounted for by level of resource.
Archives of Disease in Childhood 05/2011; 97(6):526-8. · 2.88 Impact Factor
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ABSTRACT: Cancer is the second most common cause of death in children and young people (0-19 years) accounting for 16.2% of deaths in England and Wales in 2005. Only 37.6% children and young people who died from cancer in Yorkshire were referred to Martin House Children's Hospice (MH) during the period 1990-2005. A significantly higher proportion with central nervous system tumours and a significantly lower than expected proportion with leukaemia or lymphoma were referred for palliative care. There is potential to increase the proportion of children and young people with cancer who are referred to specialist palliative care services.
Pediatric Blood & Cancer 04/2011; 56(4):677-80. · 1.89 Impact Factor
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James D McKay,
Therese Truong,
Valerie Gaborieau,
Amelie Chabrier,
Shu-Chun Chuang,
Graham Byrnes,
David Zaridze,
Oxana Shangina,
Neonila Szeszenia-Dabrowska,
Jolanta Lissowska, [......],
Doris Lechner,
Hélène Blanché,
Ivo G Gut,
Pilar Galan,
Simon Heath,
Mia Hashibe,
Richard B Hayes,
Paolo Boffetta,
Mark Lathrop,
Paul Brennan
PLoS Genetics 04/2011; 7(4). · 8.69 Impact Factor
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Sungshim Lani Park,
Yuan-Chin Amy Lee,
Manuela Marron,
Antonio Agudo,
Wolfgang Ahrens,
Luigi Barzan,
Vladimir Bencko,
Simone Benhamou,
Christine Bouchardy,
Cristina Canova, [......],
Franco Merletti,
Hermann Pohlabeln,
Lorenzo Richiardi,
Lorenzo Simonato,
Linda Sneddon,
Renato Talamini,
Dimitrios Trichopoulos,
Ariana Znaor,
Paul Brennan,
Mia Hashibe
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ABSTRACT: Previous studies reported an inverse relationship between body mass index (BMI) and upper aerodigestive tract (UADT) cancers. Examining change in BMI over time may clarify these previous observations. We used data from 2,048 cases and 2,173 hospital- and population-based controls from ten European countries (alcohol-related cancers and genetic susceptibility in Europe study) to investigate the relationship with BMI and adult change in BMI on UADT cancer risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for associations between BMI at three time intervals and BMI change on UADT cancer development, adjusting for center, age, sex, education, fruit and vegetable intake, smoking and alcohol consumption. We found an inverse relationship between UADT cancers and BMI at time of interview and 2 years before interview. No association was found with BMI at 30 years of age. Regarding BMI change between age 30 and 2 years before interview, BMI decrease (BMI change <-5%) vs. BMI stability (-5% ≤ BMI change <5%) showed no overall association with UADT cancers (OR = 1.15; 95% CI = 0.89, 1.49). An increase in BMI (BMI change ≥+5%) was inversely associated with UADT cancers (OR = 0.74; 95% CI = 0.62, 0.89). BMI gain remained inversely associated across all subsites except for esophageal cancer. When stratified by smoking or by drinking, association with BMI gain was detected only in drinkers and smokers. In conclusion, BMI gain is inversely associated with UADT cancers. These findings may be influenced by smoking and/or drinking behaviors and/or the development of preclinical UADT cancers and should be corroborated in studies of a prospective nature.
International Journal of Cancer 03/2011; 128(6):1449-61. · 5.44 Impact Factor
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James D McKay,
Therese Truong,
Valerie Gaborieau,
Amelie Chabrier,
Shu-Chun Chuang,
Graham Byrnes,
David Zaridze,
Oxana Shangina,
Neonila Szeszenia-Dabrowska,
Jolanta Lissowska, [......],
Doris Lechner,
Hélène Blanché,
Ivo G Gut,
Pilar Galan,
Simon Heath,
Mia Hashibe,
Richard B Hayes,
Paolo Boffetta,
Mark Lathrop,
Paul Brennan
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ABSTRACT: Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p ≤ 5 × 10⁻⁷). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10⁻⁸) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p =2 × 10⁻⁸) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 × 10⁻⁸); rs1229984-ADH1B, p = 7 × 10⁻⁹; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.
PLoS Genetics 03/2011; 7(3):e1001333. · 8.69 Impact Factor
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ABSTRACT: Teenage and young adult (TYA) patient care can fall into gaps between adult and children's services. Increasingly UK TYA multi-disciplinary teams manage germ cell tumors (GCT) in locally agreed collaborations and age ranges. Patterns of care are changing rapidly. However, between disciplines protocols define different assessment and management in GCT. We aimed to document changes in incidence, treatment, and survival since 1990, to record the baseline to which future trends can be compared.
Details were extracted from the UK population-based Yorkshire Specialist Cancer Register on 237 TYA aged 13-24 years diagnosed with a GCT between 1990 and 2004, followed-up until 2009. Incidence and survival patterns were assessed using Poisson and Cox regression.
Testicular (n = 190; 80%) and ovarian (n = 22; 9%) GCT were the most common malignancies, and 90% of GCT occurred aged 17-24 years. The overall incidence rate was 26.9 per million person years. Rates increased significantly by 4.0% (95% CI: 1.0-7.1%) per year on average. The most common treatment modality was surgery combined with chemotherapy (49%). Initial treatment changed significantly over time (P = 0.003) and by age (P = 0.005). There were significant differences in the management of stage 1 testicular tumors by age. Among 13- to 16-year olds, 56% were treated exclusively in adult departments. Five-year survival rates were 93-95% for gonadal GCT, and 70-75% for other sites. Survival did not differ by age (P = 0.65) or period (P = 0.41).
The age-related differences observed in the approach to GCT treatment suggest a collaborative approach to the models of care among TYA is required.
Pediatric Blood & Cancer 02/2011; 56(2):282-8. · 1.89 Impact Factor
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ABSTRACT: To investigate incidence trends of all diabetes types in all children and young people and in the south Asian subpopulation.
Annual incidence per 100,000 and time trends (1991-2006) were analyzed for 2,889 individuals aged 0-29 years diagnosed with diabetes while resident in West Yorkshire, U.K.
Diagnoses comprised type 1 (83%), type 2 (12%), maturity-onset diabetes of the young (0.7%), "J"-type/other (0.1%), and uncertain/unclassified (4%). There was a lower incidence of type 1 and a threefold excess of type 2 in south Asians compared with non-south Asians. Type 1 incidence leveled out and type 2 increased after the first south Asian case of type 2 was diagnosed in 1999. Type 2 and unclassified diabetes incidence rose in all population subgroups.
The burden of diabetes increased over time for both ethnic groups, with a significant excess of type 2 diabetes in south Asians. The rising incidence of type 1 diabetes in south Asians attenuated as type 2 diabetes increased after 1999.
Diabetes care 01/2011; 34(3):652-4. · 8.09 Impact Factor
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Tatiana V Macfarlane,
Gary J Macfarlane,
Richard J Oliver,
Simone Benhamou,
Christine Bouchardy,
Wolfgang Ahrens,
Hermann Pohlabeln,
Pagona Lagiou,
Areti Lagiou,
Xavier Castellsague, [......],
David I Conway, Patricia A McKinney,
Ariana Znaor,
Raymond J Lowry,
Peter Thomson,
Claire M Healy,
Bernard E McCartan,
Manuela Marron,
Mia Hashibe,
Paul Brennan
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ABSTRACT: The incidence of cancers of the upper aerodigestive tract (UADT) is increasing throughout the world. To date the increases have been proportionally greatest among young people. Several reports have suggested that they often do not have a history of tobacco smoking or heavy alcohol consumption.
To determine the contribution of lifestyle factors to the etiology of UADT cancers occurring in those aged less than 50 years.
A case-control study was conducted in 10 European countries. Cases were cancers of the oral cavity and pharynx, larynx and esophagus, and hospital or population controls were age and sex matched.
There were 356 cases younger than 50 years and 419 controls. Risk was strongly related to current smoking [odds ratio (OR) 5.5 95%; confidence interval (CI) (3.3, 9.2)], and risk increased with number of pack-years smoked. Risk was also related to alcohol consumption for both current (OR 1.8; 0.97, 3.3) and past (OR 3.4; 1.6, 7.4) drinkers, and risk increased with number of drink-years. Persons frequently consuming fruits and vegetables were at significantly reduced risk.
Risk factors already identified as being important for UADT cancers in adults are also important influences on risk in younger adults. The implication of these results is that the public health message in preventing UADT cancers remains the same to young and old alike.
Cancer Causes and Control 12/2010; 21(12):2213-21. · 2.88 Impact Factor
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Judith A Schwartzbaum,
Yuanyuan Xiao,
Yanhong Liu,
Spyros Tsavachidis,
Mitchel S Berger,
Melissa L Bondy,
Jeffrey S Chang,
Susan M Chang,
Paul A Decker,
Bo Ding, [......],
Michael Prados,
Terri Rice,
Lindsay B Robertson,
Minouk J Schoemaker,
Sanjay Shete,
Anthony J Swerdlow,
Joe L Wiemels,
John K Wiencke,
Ping Yang,
Margaret R Wrensch
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ABSTRACT: To determine whether inherited variations in immune function single-nucleotide polymorphisms (SNPs), genes or pathways affect glioblastoma risk, we analyzed data from recent genome-wide association studies in conjunction with predefined immune function genes and pathways. Gene and pathway analyses were conducted on two independent data sets using 6629 SNPs in 911 genes on 17 immune pathways from 525 glioblastoma cases and 602 controls from the University of California, San Francisco (UCSF) and a subset of 6029 SNPs in 893 genes from 531 cases and 1782 controls from MD Anderson (MDA). To further assess consistency of SNP-level associations, we also compared data from the UK (266 cases and 2482 controls) and the Mayo Clinic (114 cases and 111 controls). Although three correlated epidermal growth factor receptor (EGFR) SNPs were consistently associated with glioblastoma in all four data sets (Mantel-Haenzel P values = 1 × 10⁻⁵ to 4 × 10⁻³), independent replication is required as genome-wide significance was not attained. In gene-level analyses, eight immune function genes were significantly (minP < 0.05) associated with glioblastoma; the IL-2RA (CD25) cytokine gene had the smallest minP values in both UCSF (minP = 0.01) and MDA (minP = 0.001) data sets. The IL-2RA receptor is found on the surface of regulatory T cells potentially contributing to immunosuppression characteristic of the glioblastoma microenvironment. In pathway correlation analyses, cytokine signaling and adhesion-extravasation-migration pathways showed similar associations with glioblastoma risk in both MDA and UCSF data sets. Our findings represent the first systematic description of immune genes and pathways that characterize glioblastoma risk.
Carcinogenesis 10/2010; 31(10):1770-7. · 5.70 Impact Factor
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ABSTRACT: Early life infection has been implicated in the aetiology of many chronic diseases, most often through proxy measures. Data on ten infectious symptoms were collected by parental questionnaire when children were 6 months old as part of the Avon Longitudinal Study of Parents and Children, United Kingdom. A latent class analysis was used to identify patterns of infection and their relationship to five factors commonly used as proxies: sex, other children in the home, maternal smoking, breastfeeding and maternal education. A total of 10,032 singleton children were included in the analysis. Five classes were identified with differing infectious disease patterns and children were assigned to the class for which they had a highest probability of membership based on their infectious symptom profile: 'general infection' (n = 1,252, 12.5%), 'gastrointestinal' (n = 1,902, 19.0%), 'mild respiratory' (n = 3,560, 35.5%), 'colds/ear ache' (n = 462, 4.6%) and 'healthy' (n = 2,856, 28.5%). Females had a reduced risk of being in all infectious classes, other children in the home were associated with an increased risk of being in the 'general infection', 'mild respiratory' or 'colds/ear ache' class. Breastfeeding reduced the risk of being in the 'general infection' and 'gastrointestinal' classes whereas maternal smoking increased the risk of membership. Higher maternal education was associated with an increased risk of being in the 'mild respiratory' group. Other children in the home had the greatest association with infectious class membership. Latent class analysis provided a flexible method of investigating the relationship between multiple symptoms and demographic and lifestyle factors.
European Journal of Epidemiology 10/2010; 25(12):875-83. · 4.71 Impact Factor
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Minouk J Schoemaker,
Lindsay Robertson,
Annette Wigertz,
Michael E Jones,
Fay J Hosking,
Maria Feychting,
Stefan Lönn, Patricia A McKinney,
Sarah J Hepworth,
Kenneth R Muir,
Anssi Auvinen,
Tiina Salminen,
Anne Kiuru,
Christoffer Johansen,
Richard S Houlston,
Anthony J Swerdlow
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ABSTRACT: The etiology of glioma is barely known. Epidemiologic studies have provided evidence for an inverse relation between glioma risk and allergic disease. Genome-wide association data have identified common genetic variants at 5p15.33 (rs2736100, TERT), 8q24.21 (rs4295627, CCDC26), 9p21.3 (rs4977756, CDKN2A-CDKN2B), 11q23.3 (rs498872, PHLDB1), and 20q13.33 (rs6010620, RTEL1) as determinants of glioma risk. The authors investigated whether there is interaction between the effects of allergy and these 5 variants on glioma risk. Data from 5 case-control studies carried out in Denmark, Finland, Sweden, and the United Kingdom (2000-2004) were used, totaling 1,029 cases and 1,668 controls. Risk was inversely associated with asthma, hay fever, eczema, and "any allergy," significantly for each factor except asthma, and was significantly positively associated with number of risk alleles for each of the 5 single nucleotide polymorphisms. There was interaction between asthma and rs498872 (greater protective effect of asthma with increasing number of risk alleles; per-allele interaction odds ratio (OR) = 0.65, P = 0.041), between "any allergy" and rs4977756 (smaller protective effect; interaction OR = 1.27, P = 0.047), and between "any allergy" and rs6010620 (greater protective effect; interaction OR = 0.70, P = 0.017). Case-only analyses provided further support for atopy interactions for rs4977756 and rs498872. This study provides evidence for possible gene-environment interactions in glioma development.
American journal of epidemiology 06/2010; 171(11):1165-73. · 5.59 Impact Factor
