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ABSTRACT: This study examined cancer incidence (1986-2008) and mortality (1986-2011) among the Estonian Chernobyl cleanup workers in comparison with the Estonian male population. The cohort of 4810 men was followed through nationwide population, mortality and cancer registries. Cancer and death risks were measured by standardised incidence ratio (SIR) and standardised mortality ratio (SMR), respectively. Poisson regression was used to analyse the effects of year of arrival, duration of stay and time since return on cancer and death risks. The SIR for all cancers was 1.06 with 95% confidence interval 0.93-1.20 (232 cases). Elevated risks were found for cancers of the pharynx, the oesophagus and the joint category of alcohol-related sites. No clear evidence of an increased risk of thyroid cancer, leukaemia or radiation-related cancer sites combined was apparent. The SMR for all causes of death was 1.02 with 95% confidence interval 0.96-1.08 (1018 deaths). Excess mortality was observed for mouth and pharynx cancer, alcohol-related cancer sites together and suicide. Duration of stay rather than year of arrival was associated with increased mortality. Twenty-six years of follow-up of this cohort indicates no definite health effects attributable to radiation, but the elevated suicide risk has persisted.
Journal of Radiological Protection 03/2013; 33(2):395-411. · 1.39 Impact Factor
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Stephanie A Kovalchik,
Cécile M Ronckers,
Lene H S Veiga,
Alice J Sigurdson, Peter D Inskip,
Florent de Vathaire,
Charles A Sklar,
Sarah S Donaldson,
Harald Anderson,
Parveen Bhatti,
Sue Hammond,
Wendy M Leisenring,
Ann C Mertens,
Susan A Smith,
Marilyn Stovall,
Margaret A Tucker,
Rita E Weathers,
Leslie L Robison,
Ruth M Pfeiffer
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ABSTRACT: PURPOSEWe developed three absolute risk models for second primary thyroid cancer to assist with long-term clinical monitoring of childhood cancer survivors. PATIENTS AND METHODS
We used data from the Childhood Cancer Survivor Study (CCSS) and two nested case-control studies (Nordic CCSS; Late Effects Study Group). Model M1 included self-reported risk factors, model M2 added basic radiation and chemotherapy treatment information abstracted from medical records, and model M3 refined M2 by incorporating reconstructed radiation absorbed dose to the thyroid. All models were validated in an independent cohort of French childhood cancer survivors.ResultsM1 included birth year, initial cancer type, age at diagnosis, sex, and past thyroid nodule diagnosis. M2 added radiation (yes/no), radiation to the neck (yes/no), and alkylating agent (yes/no). Past thyroid nodule was consistently the strongest risk factor (M1 relative risk [RR ], 10.8; M2 RR, 6.8; M3 RR, 8.2). In the validation cohort, 20-year absolute risk predictions for second primary thyroid cancer ranged from 0.04% to 7.4% for M2. Expected events agreed well with observed events for each model, indicating good calibration. All models had good discriminatory ability (M1 area under the receiver operating characteristics curve [AUC ], 0.71; 95% CI, 0.64 to 0.77; M2 AUC, 0.80; 95% CI, 0.73 to 0.86; M3 AUC, 0.75; 95% CI, 0.69 to 0.82). CONCLUSION
We developed and validated three absolute risk models for second primary thyroid cancer. Model M2, with basic prior treatment information, could be useful for monitoring thyroid cancer risk in childhood cancer survivors.
Journal of Clinical Oncology 11/2012; · 18.37 Impact Factor
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ABSTRACT: Chlorinated solvents are classified as probable or possible carcinogens. It is unknown whether exposure to these agents increases the risk of malignant or benign brain tumours. Our objective was to evaluate associations of brain tumour risk with occupational exposure to six chlorinated solvents (ie, dichloromethane, chloroform, carbon tetrachloride, 1,1,1-trichloroethane, trichloroethylene and perchloroethylene).
489 glioma cases, 197 meningioma cases and 799 controls were enrolled in a hospital-based case-control study conducted at three USA hospitals in Arizona, Massachusetts and Pennsylvania. Information about occupational history was obtained through a detailed inperson interview that included job-specific modules of questions such that the interview was tailored to each individual's particular work history. An industrial hygienist assessed potential solvent exposure based on this information and an exhaustive review of the relevant industrial hygiene literature. Unconditional logistic regression models were used to calculate OR and 95% CI for each solvent for ever/never, duration, cumulative, average weekly and highest exposure.
Overall, we found no consistent evidence of an increased risk of glioma or meningioma related to occupational exposure to the six chlorinated solvents evaluated. There was some suggestion of an association between carbon tetrachloride and glioma in analyses restricted to exposed subjects, with average weekly exposure above the median associated with increased risk compared with below the median exposure (OR = 7.1, 95% CI 1.1 to 45.2).
We found no consistent evidence for increased brain tumour risk related to chlorinated solvents.
Occupational and environmental medicine 08/2012; 69(11):793-801. · 3.64 Impact Factor
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ABSTRACT: The purpose of this study is to quantify cancer mortality in relationship to organ-specific radiation dose among women irradiated for benign gynecologic disorders. Included in this study are 12,955 women treated for benign gynecologic disorders at hospitals in the Northeastern U.S. between 1925 and 1965; 9,770 women treated by radiation and 3,186 women treated by other methods. The average age at treatment was 45.9 years (range, 13-88 years), and the average follow-up period was 30.1 years (maximum, 69.9 years). Radiation doses to organs and active bone marrow were reconstructed by medical physicists using original radiotherapy records. The highest doses were received by the uterine cervix (median, 120 Gy) and uterine corpus (median, 34 Gy), followed by the bladder, rectum and colon (median, 1.7-7.2 Gy), with other abdominal organs receiving median doses ≤1 Gy and organs in the chest and head receiving doses <0.1 Gy. Standardized mortality rate ratios relative to the general U.S. population were calculated. Radiation-related risks were estimated in internal analyses using Poisson regression models. Mortality was significantly elevated among irradiated women for cancers of the uterine corpus, ovary, bladder, rectum, colon and brain, as well as for leukemia (exclusive of chronic lymphocytic leukemia) but not for cancer of the cervix, Hodgkin or non-Hodgkin lymphoma, multiple myeloma, or chronic lymphocytic leukemia. Evidence of a dose-response was seen for cancers of the ovary [excess relative risk (ERR) = 0.31/Gy, P < 0.001], bladder (ERR = 0.21/Gy, P = 0.02) and rectum (ERR = 0.23/Gy, P = 0.05) and suggested for colon (ERR = 0.09/Gy, P = 0.10), but not for cancers of the uterine corpus or brain nor for non-chronic lymphocytic leukemia. Relative risks of mortality due to cancers of the stomach, pancreas, liver and kidney were close to 1.0, with no evidence of dose-response over the range of 0-1.5 Gy. Breast cancer was not significantly associated with dose to the breast or ovary. Mortality due to cancers of heavily irradiated organs remained elevated up to 40 years after irradiation. Significantly elevated radiation-related risk was seen for cancers of organs proximal to the radiation source or fields (bladder, rectum and ovary), as well as for non-chronic lymphocytic leukemia. Our results corroborate those from previous studies that suggest that cells of the uterine cervix and lymphopoietic system are relatively resistant to the carcinogenic effects of radiation. Studies of women irradiated for benign gynecologic disorders, together with studies of women treated with higher doses of radiation for uterine cancers, provide quantitative information on cancer risks associated with a broad range of pelvic radiation exposures.
Radiation Research 08/2012; 178(4):266-79. · 2.68 Impact Factor
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ABSTRACT: Basal cell carcinoma (BCC) is the most common malignancy in the United States. Ionizing radiation is an established risk factor in certain populations, including cancer survivors. We quantified the association between ionizing radiation dose and the risk of BCC in childhood cancer survivors.
Participants in the Childhood Cancer Survivor Study who reported a BCC (case subjects, n = 199) were matched on age and length of follow-up to three study participants who had not developed a BCC (control subjects, n = 597). The radiation-absorbed dose (in Gy) to the BCC location was calculated based on individual radiotherapy records using a custom-designed dosimetry program. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between demographic and treatment factors, therapeutic radiation dose, and surrogate markers of sun sensitivity (skin and hair color) and the risk of BCC. A linear dose-response model was fitted to evaluate the excess odds ratio per Gy of radiation dose.
Among case subjects, 83% developed BCC between the ages of 20 and 39 years. Radiation therapy, either alone or in combination with chemotherapy, was associated with an increased risk of BCC compared with no chemotherapy or radiation. The odds ratio for subjects who received 35 Gy or more to the skin site vs no radiation therapy was 39.8 (95% CI = 8.6 to 185). Results were consistent with a linear dose-response relationship, with an excess odds ratio per Gy of 1.09 (95% CI = 0.49 to 2.64). No other treatment variables were statistically significantly associated with an increased risk of BCC.
Radiation doses to the skin of more than 1 Gy are associated with an increased risk of BCC.
CancerSpectrum Knowledge Environment 07/2012; 104(16):1240-50. · 14.07 Impact Factor
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Houda Boukheris,
Marilyn Stovall,
Ethel S Gilbert,
Kayla L Stratton,
Susan A Smith,
Rita Weathers,
Sue Hammond,
Ann C Mertens,
Sarah S Donaldson,
Gregory T Armstrong,
Leslie L Robison,
Joseph P Neglia, Peter D Inskip
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ABSTRACT: PURPOSE: To evaluate effects of radiation therapy, chemotherapy, cigarette smoking, and alcohol consumption on the risk of second primary salivary gland cancer (SGC) in the Childhood Cancer Survivor Study (CCSS). METHODS AND MATERIALS: Standardized incidence ratios (SIR) and excess absolute risks (EAR) of SGC in the CCSS were calculated using incidence rates from Surveillance, Epidemiology, and End Results population-based cancer registries. Radiation dose to the salivary glands was estimated based on medical records. Poisson regression was used to assess risks with respect to radiation dose, chemotherapy, smoking, and alcohol consumption. RESULTS: During the time period of the study, 23 cases of SGC were diagnosed among 14,135 childhood cancer survivors. The mean age at diagnosis of the first primary cancer was 8.3 years, and the mean age at SGC diagnosis was 24.8 years. The incidence of SGC was 39-fold higher in the cohort than in the general population (SIR = 39.4; 95% CI = 25.4-57.8). The EAR was 9.8 per 100,000 person-years. Risk increased linearly with radiation dose (excess relative risk = 0.36/Gy; 95% CI = 0.06-2.5) and remained elevated after 20 years. There was no significant trend of increasing risk with increasing dose of chemotherapeutic agents, pack-years of cigarette smoking, or alcohol intake. CONCLUSION: Although the cumulative incidence of SGC was low, childhood cancer survivors treated with radiation experienced significantly increased risk for at least 2 decades after exposure, and risk was positively associated with radiation dose. Results underscore the importance of long-term follow up of childhood cancer survivors for the development of new malignancies.
International journal of radiation oncology, biology, physics 07/2012; · 4.59 Impact Factor
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Tara O Henderson,
Preetha Rajaraman,
Marilyn Stovall,
Louis S Constine,
Aliza Olive,
Susan A Smith,
Ann Mertens,
Anna Meadows,
Joseph P Neglia,
Sue Hammond,
John Whitton, Peter D Inskip,
Leslie L Robison,
Lisa Diller
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ABSTRACT: Childhood cancer survivors have an increased risk of secondary sarcomas. To better identify those at risk, the relationship between therapeutic dose of chemotherapy and radiation and secondary sarcoma should be quantified.
We conducted a nested case-control study of secondary sarcomas (105 cases, 422 matched controls) in a cohort of 14,372 childhood cancer survivors. Radiation dose at the second malignant neoplasm (SMN) site and use of chemotherapy were estimated from detailed review of medical records. Odds ratios (ORs) and 95% confidence intervals were estimated by conditional logistic regression. Excess odds ratio (EOR) was modeled as a function of radiation dose, chemotherapy, and host factors.
Sarcomas occurred a median of 11.8 years (range, 5.3-31.3 years) from original diagnosis. Any exposure to radiation was associated with increased risk of secondary sarcoma (OR = 4.1, 95% CI = 1.8-9.5). A dose-response relation was observed, with elevated risks at doses between 10 and 29.9 Gy (OR = 15.6, 95% CI = 4.5-53.9), 30-49.9 Gy (OR = 16.0, 95% CI 3.8-67.8) and >50 Gy (OR = 114.1, 95% CI 13.5-964.8). Anthracycline exposure was associated with sarcoma risk (OR = 3.5, 95% CI = 1.6-7.7) adjusting for radiation dose, other chemotherapy, and primary cancer. Adjusting for treatment, survivors with a first diagnosis of Hodgkin lymphoma (OR = 10.7, 95% CI = 3.1-37.4) or primary sarcoma (OR = 8.4, 95% CI = 3.2-22.3) were more likely to develop a sarcoma.
Of the risk factors evaluated, radiation exposure was the most important for secondary sarcoma development in childhood cancer survivors; anthracycline chemotherapy exposure was also associated with increased risk.
International journal of radiation oncology, biology, physics 07/2012; 84(1):224-30. · 4.59 Impact Factor
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Lene H S Veiga,
Parveen Bhatti,
Cécile M Ronckers,
Alice J Sigurdson,
Marilyn Stovall,
Susan A Smith,
Rita Weathers,
Wendy Leisenring,
Ann C Mertens,
Sue Hammond,
Joseph P Neglia,
Anna T Meadows,
Sarah S Donaldson,
Charles A Sklar,
Debra L Friedman,
Leslie L Robison, Peter D Inskip
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ABSTRACT: Although ionizing radiation is an established environmental risk factor for thyroid cancer, the effect of chemotherapy drugs on thyroid cancer risk remains unclear. We evaluated the chemotherapy-related risk of thyroid cancer in childhood cancer survivors and the possible joint effects of chemotherapy and radiotherapy.
The study included 12,547 five-year survivors of childhood cancer diagnosed during 1970 through 1986. Chemotherapy and radiotherapy information was obtained from medical records, and radiation dose was estimated to the thyroid gland. Cumulative incidence and relative risks were calculated with life-table methods and Poisson regression. Chemotherapy-related risks were evaluated separately by categories of radiation dose.
Histologically confirmed thyroid cancer occurred in 119 patients. Thirty years after the first childhood cancer treatment, the cumulative incidence of thyroid cancer was 1.3% (95% CI, 1.0-1.6) for females and 0.6% (0.4-0.8) for males. Among patients with thyroid radiation doses of 20 Gy or less, treatment with alkylating agents was associated with a significant 2.4-fold increased risk of thyroid cancer (95% CI, 1.3-4.5; P = 0.002). Chemotherapy risks decreased as radiation dose increased, with a significant decrease for patients treated with alkylating agents (P(trend) = 0.03). No chemotherapy-related risk was evident for thyroid radiation doses more than 20 Gy.
Treatments with alkylating agents increased thyroid cancer risk, but only in the radiation dose range less than 20 Gy, in which cell sparing likely predominates over cell killing.
Our study adds to the evidence for chemotherapy agent-specific increased risks of thyroid cancer, which to date, were mainly thought to be related to prior radiotherapy.
Cancer Epidemiology Biomarkers & Prevention 01/2012; 21(1):92-101. · 4.12 Impact Factor
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Sophia S Wang,
Patricia Hartge,
Meredith Yeager,
Tania Carreón,
Avima M Ruder,
Martha Linet, Peter D Inskip,
Amanda Black,
Ann W Hsing,
Michael Alavanja,
Laura Beane-Freeman,
Mahboobeh Safaiean,
Stephen J Chanock,
Preetha Rajaraman
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ABSTRACT: In a pooled analysis of 4 US epidemiologic studies (1993-2001), the authors evaluated the role of 5 female reproductive factors in 357 women with glioma and 822 controls. The authors further evaluated the independent association between 5 implicated gene variants and glioma risk among the study population, as well as the joint associations of female reproductive factors (ages at menarche and menopause, menopausal status, use of oral contraceptives, and menopausal hormone therapy) and these gene variants on glioma risk. Risk estimates were calculated as odds ratios and 95% confidence intervals that were adjusted for age, race, and study. Three of the gene variants (rs4295627, a variant of CCDC26; rs4977756, a variant of CDKN2A and CDKN2B; and rs6010620, a variant of RTEL1) were statistically significantly associated with glioma risk in the present population. Compared with women who had an early age at menarche (<12 years of age), those who reported menarche at 12-13 years of age or at 14 years of age or older had a 1.7-fold higher risk and a 1.9-fold higher risk of glioma, respectively (P for trend = 0.009). Postmenopausal women and women who reported ever having used oral contraceptives had a decreased risk of glioma. The authors did not observe joint associations between these reproductive characteristics and the implicated glioma gene variants. These results require replication, but if confirmed, they would suggest that the gene variants that have previously been implicated in the development of glioma are unlikely to act through the same hormonal mechanisms in women.
American journal of epidemiology 09/2011; 174(8):901-8. · 5.59 Impact Factor
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ABSTRACT: Several case-control studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs) reduce risk for glioblastoma, an aggressive form of brain cancer. Prospective investigations have not observed such an association, but these studies lacked adequate brain cancer case numbers and did not stratify by histologic subtype. We prospectively investigated the association between NSAID use and risk of all glioma as well as the risk of glioblastoma subtype in the National Institutes of Health (NIH)-AARP Diet and Health Study. The frequency of aspirin and nonaspirin NSAID use 1 year prior to baseline was ascertained using a self-administered questionnaire. Hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using Cox regression models with age as the underlying time metric, adjusted for sex, race, and history of heart disease. The analysis included 302,767 individuals, with 341 incident glioma cases (264 glioblastoma). No association was observed between regular use (>2 times/wk) of aspirin and risk of glioma (HR = 1.16; 95% CI, 0.87-1.56) or glioblastoma (HR = 1.17; 95% CI, 0.83-1.64) as compared with no use. Null associations were also observed for nonaspirin NSAID use (HR for glioma = 0.90; 95% CI, 0.65-1.25 and HR for glioblastoma = 0.83; 95% CI, 0.56-1.20) as compared with no use. Our findings from this large prospective study do not support an inverse association between NSAIDs and risk of all glioma or glioblastoma.
Cancer Prevention Research 09/2011; 4(12):2027-34. · 4.91 Impact Factor
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ABSTRACT: Although incidence of colorectal cancer (CRC) in the United States has declined in recent years, rates remain higher in men than in women and the male-to-female incidence rate ratio (MF IRR) increases progressively across the colon from the cecum to the rectum. Rates among races/ethnicities other than Whites or Blacks have not been frequently reported. To examine CRC rates by sex across anatomic subsite, age and racial/ethnic groups, we used the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program for cases diagnosed among residents of 13 registries during 1992-2006. Incidence rates were expressed per 100,000 person-years and age-adjusted to the 2000 US Standard Population; MF IRR and 95% confidence intervals were also calculated. Among each racial/ethnic group, the MF IRR increased fairly monotonically from close to unity for cecal cancers to 1.81 (Hispanics) for rectal cancers. MF IRRs increased with age most rapidly for distal colon cancers from <1.0 at ages <50 years to 1.4-1.9 at older ages. The MF IRR for rectal cancers also rose with age from about 1.0 to 2.0. For proximal cancer, the MF IRR was consistently <1.5; among American Indian/Alaska Natives, it was <1.0 across all ages. The MF IRRs for CRC vary markedly according to subsite and age but less by racial/ethnic group. These findings may partially reflect differences in screening experiences and access to medical care but also suggest that etiologic factors may be playing a role.
International Journal of Cancer 04/2011; 128(7):1668-75. · 5.44 Impact Factor
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Bridget J McCarthy,
Kristin M Rankin,
Ken Aldape,
Melissa L Bondy,
Thomas Brännström,
Helle Broholm,
Maria Feychting,
Dora Il'yasova, Peter D Inskip,
Christoffer Johansen,
Beatrice S Melin,
Avima M Ruder,
Mary Ann Butler,
Michael E Scheurer,
Joachim Schüz,
Judith A Schwartzbaum,
Margaret R Wrensch,
Faith G Davis
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ABSTRACT: Oligodendroglial tumors are rare subtypes of brain tumors and are often combined with other glial tumors in epidemiological analyses. However, different demographic associations and clinical characteristics suggest potentially different risk factors. The purpose of this study was to investigate possible risk factors for oligodendroglial tumors (including oligodendroglioma, anaplastic oligodendroglioma, and mixed glioma). Data from 7 case-control studies (5 US and 2 Scandinavian) were pooled. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for age group, gender, and study site. Data on 617 cases and 1260 controls were available for analyses. Using data from all 7 studies, history of allergies and/or asthma was associated with a decreased risk of anaplastic oligodendroglioma (OR = 0.6; 95% CI: 0.4-0.9), and history of asthma only was associated with a decreased risk of oligodendroglioma (OR = 0.5; 95% CI: 0.3-0.9) and anaplastic oligodendroglioma (OR = 0.3; 95% CI: 0.1-0.9). A family history of brain tumors was associated with an increased risk of anaplastic oligodendroglioma (OR = 2.2; 95% CI: 1.1-4.5). Having had chicken pox was associated with a decreased risk of oligodendroglioma (OR = 0.6; 95% CI: 0.4-0.9) and anaplastic oligodendroglioma (OR = 0.5; 95% CI: 0.3-0.9) in the US studies. Although there is some overlap in risk factors between oligodendroglial tumors and gliomas as a group, it is likely that additional factors specific to oligodendroglial tumors have yet to be identified. Large, multi-institution international studies will be necessary to better characterize these etiological risk factors.
Neuro-Oncology 02/2011; 13(2):242-50. · 5.72 Impact Factor
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ABSTRACT: There is great interest in evaluating gene-environment interactions with chemical exposures, but exposure assessment poses a unique challenge in case-control studies. Expert assessment of detailed work history data is usually considered the best approach, but it is a laborious and time-consuming process. We set out to determine if a less intensive method of exposure assessment (a job exposure matrix (JEM)) would produce similar results to a previous analysis that found evidence of effect modification of the association between expert-assessed lead exposure and risk of brain tumours by a single nucleotide polymorphism in the ALAD gene (rs1800435).
We used data from a study of 355 patients with glioma, 151 patients with meningioma and 505 controls. Logistic regression models were used to examine associations between brain tumour risk and lead exposure and effect modification by genotype. We evaluated Cohen's κ, sensitivity and specificity for the JEM compared to the expert-assessed exposure metrics.
Although effect estimates were imprecise and driven by a small number of cases, we found evidence of effect modification between lead exposure and ALAD genotype when using expert- but not JEM-derived lead exposure estimates. κ Values indicated only modest agreement (<0.5) for the exposure metrics, with the JEM indicating high specificity (∼0.9) but poor sensitivity (∼0.5). Disagreement between the two methods was generally due to having additional information in the detailed work history.
These results provide preliminary evidence suggesting that high quality exposure data are likely to improve the ability to detect genetic effect modification.
Occupational and environmental medicine 01/2011; 68(1):4-9. · 3.64 Impact Factor
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ABSTRACT: Few studies have examined the relationship between human leukocyte antigen (HLA) polymorphisms and adult glioma, particularly at class II loci. We evaluated the association between selected HLA class II polymorphisms and adult glioma in a large, hospital-based case-control study, using unconditional logistic regression. DQB1 06 (OR=1.67, 95% CI=1.17-2.39) and DRB1 13 (OR=1.69, 95% CI=1.08-2.64) alleles were associated with an increased risk of glioma, while the DQB1 05 allele showed an inverse association (OR=0.63, 95% CI=0.43-0.93). These results, which were of borderline significance once controlled for the false discovery rate, suggest a potential role for the DQB1 06, DQB1 05, and DRB1 13 alleles in glioma susceptibility.
Journal of neuroimmunology 12/2010; 233(1-2):185-91. · 2.84 Impact Factor
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Parveen Bhatti,
Lene H S Veiga,
Cécile M Ronckers,
Alice J Sigurdson,
Marilyn Stovall,
Susan A Smith,
Rita Weathers,
Wendy Leisenring,
Ann C Mertens,
Sue Hammond,
Debra L Friedman,
Joseph P Neglia,
Anna T Meadows,
Sarah S Donaldson,
Charles A Sklar,
Leslie L Robison, Peter D Inskip
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ABSTRACT: Previous studies have indicated that thyroid cancer risk after a first childhood malignancy is curvilinear with radiation dose, increasing at low to moderate doses and decreasing at high doses. Understanding factors that modify the radiation dose response over the entire therapeutic dose range is challenging and requires large numbers of subjects. We quantified the long-term risk of thyroid cancer associated with radiation treatment among 12,547 5-year survivors of a childhood cancer (leukemia, Hodgkin lymphoma and non-Hodgkin lymphoma, central nervous system cancer, soft tissue sarcoma, kidney cancer, bone cancer, neuroblastoma) diagnosed between 1970 and 1986 in the Childhood Cancer Survivor Study using the most current cohort follow-up to 2005. There were 119 subsequent pathologically confirmed thyroid cancer cases, and individual radiation doses to the thyroid gland were estimated for the entire cohort. This cohort study builds on the previous case-control study in this population (69 thyroid cancer cases with follow-up to 2000) by allowing the evaluation of both relative and absolute risks. Poisson regression analyses were used to calculate standardized incidence ratios (SIR), excess relative risks (ERR) and excess absolute risks (EAR) of thyroid cancer associated with radiation dose. Other factors such as sex, type of first cancer, attained age, age at exposure to radiation, time since exposure to radiation, and chemotherapy (yes/no) were assessed for their effect on the linear and exponential quadratic terms describing the dose-response relationship. Similar to the previous analysis, thyroid cancer risk increased linearly with radiation dose up to approximately 20 Gy, where the relative risk peaked at 14.6-fold (95% CI, 6.8-31.5). At thyroid radiation doses >20 Gy, a downturn in the dose-response relationship was observed. The ERR model that best fit the data was linear-exponential quadratic. We found that age at exposure modified the ERR linear dose term (higher radiation risk with younger age) (P < 0.001) and that sex (higher radiation risk among females) (P = 0.008) and time since exposure (higher radiation risk with longer time) (P < 0.001) modified the EAR linear dose term. None of these factors modified the exponential quadratic (high dose) term. Sex, age at exposure and time since exposure were found to be significant modifiers of the radiation-related risk of thyroid cancer and as such are important factors to account for in clinical follow-up and thyroid cancer risk estimation among childhood cancer survivors.
Radiation Research 12/2010; 174(6):741-52. · 2.68 Impact Factor
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ABSTRACT: The use of cellular telephones has grown explosively during the past two decades, and there are now more than 279 million wireless subscribers in the United States. If cellular phone use causes brain cancer, as some suggest, the potential public health implications could be considerable. One might expect the effects of such a prevalent exposure to be reflected in general population incidence rates, unless the induction period is very long or confined to very long-term users. To address this issue, we examined temporal trends in brain cancer incidence rates in the United States, using data collected by the Surveillance, Epidemiology, and End Results (SEER) Program. Log-linear models were used to estimate the annual percent change in rates among whites. With the exception of the 20-29-year age group, the trends for 1992-2006 were downward or flat. Among those aged 20-29 years, there was a statistically significant increasing trend between 1992 and 2006 among females but not among males. The recent trend in 20-29-year-old women was driven by a rising incidence of frontal lobe cancers. No increases were apparent for temporal or parietal lobe cancers, or cancers of the cerebellum, which involve the parts of the brain that would be more highly exposed to radiofrequency radiation from cellular phones. Frontal lobe cancer rates also rose among 20-29-year-old males, but the increase began earlier than among females and before cell phone use was highly prevalent. Overall, these incidence data do not provide support to the view that cellular phone use causes brain cancer.
Neuro-Oncology 11/2010; 12(11):1147-51. · 5.72 Impact Factor
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Preetha Rajaraman,
Alina V Brenner,
Gila Neta,
Ruth Pfeiffer,
Sophia S Wang,
Meredith Yeager,
Gilles Thomas,
Howard A Fine,
Martha S Linet,
Nathaniel Rothman,
Stephen J Chanock, Peter D Inskip
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ABSTRACT: The etiology of meningioma, the second most common type of adult brain tumor in the United States, is largely unknown. Prior studies indicate that history of immune-related conditions may affect the risk of meningioma.
To identify genetic markers for meningioma in genes involved with innate immunity, we conducted an exploratory association study of 101 meningioma cases and 330 frequency-matched controls of European ancestry using subjects from a hospital-based study conducted by the National Cancer Institute. We genotyped 1,407 "tag" single nucleotide polymorphisms (SNP) in 148 genetic regions chosen on the basis of an r2>0.8 and minor allele frequency of >5% in Caucasians in HapMap1. Risk of meningioma was estimated by odds ratios and 95% confidence intervals.
Seventeen SNPs distributed across 12 genetic regions (NFKB1 (3), FCER1G (3), CCR6 (2), VCAM1, CD14, TNFRSF18, RAC2, XDH, C1D, TLR1/TLR10/TLR6, NOS1, and DEFA5) were associated with the risk of meningioma with P<0.01. Although individual SNP tests were not significant after controlling for multiple comparisons, gene region-based tests were statistically significant (P<0.05) for TNFRSF18, NFKB1, FCER1G, CD14, C1D, CCR6, and VCAM1.
Our results indicate that common genetic polymorphisms in innate immunity genes may be associated with risk of meningioma. Given the small sample size, replication of these results in a larger study of meningioma is needed.
Cancer Epidemiology Biomarkers & Prevention 05/2010; 19(5):1356-61. · 4.12 Impact Factor
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Preetha Rajaraman,
Amy Hutchinson,
Sara Wichner,
Peter M Black,
Howard A Fine,
Jay S Loeffler,
Robert G Selker,
William R Shapiro,
Nathaniel Rothman,
Martha S Linet, Peter D Inskip
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ABSTRACT: Although the etiology of primary brain tumors is largely unknown, prior studies suggest that DNA repair polymorphisms may influence risk of glioma. Altered DNA repair is also likely to affect the risk of meningioma and acoustic neuroma, but these tumors have not been well studied. We estimated the risk of glioma (n = 362), meningioma (n = 134), and acoustic neuroma (n = 69) in non-Hispanic whites with respect to 36 single nucleotide polymorphisms from 26 genes involved in DNA repair in a hospital-based, case-control study conducted by the National Cancer Institute. We observed significantly increased risk of meningioma with the T variant of GLTSCR1 rs1035938 (OR(CT/TT) = 3.5; 95% confidence interval: 1.8-6.9; P(trend) .0006), which persisted after controlling for multiple comparisons (P = .019). Significantly increased meningioma risk was also observed for the minor allele variants of ERCC4 rs1800067 (P(trend) .01); MUTYH rs3219466 (P(trend) .02), and PCNA rs25406 (P(trend) .03). The NBN rs1805794 minor allele variant was associated with decreased meningioma risk (P(trend) .006). Risk of acoustic neuroma was increased for the ERCC2 rs1799793 (P(trend) .03) and ERCC5 rs17655 (P(trend) .05) variants and decreased for the PARP1 rs1136410 (P(trend) .03). Decreased glioma risk was observed with the XRCC1 rs1799782 variant (P(trend) .04). Our results suggest that common DNA repair variants may affect the risk of adult brain tumors, especially meningioma.
Neuro-Oncology 01/2010; 12(1):37-48. · 5.72 Impact Factor
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Peter D Inskip,
Leslie L Robison,
Marilyn Stovall,
Susan A Smith,
Sue Hammond,
Ann C Mertens,
John A Whitton,
Lisa Diller,
Lisa Kenney,
Sarah S Donaldson,
Anna T Meadows,
Joseph P Neglia
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ABSTRACT: The purpose of this study was to quantify the risk of breast cancer in relation to radiation dose and chemotherapy among survivors of childhood cancer.
We conducted a case-control study of breast cancer in a cohort of 6,647 women who were 5-year survivors of childhood cancer and who were treated during 1970 through 1986. One hundred twenty patients with histologically confirmed breast cancer were identified and were individually matched to four selected controls on age at initial cancer and time since initial cancer. Medical physicists estimated radiation dose to the breast tumor site and ovaries on the basis of medical records.
The odds ratio for breast cancer increased linearly with radiation dose, and it reached 11-fold for local breast doses of approximately 40 Gy relative to no radiation (P for trend < .0001). Risk associated with breast irradiation was sharply reduced among women who received 5 Gy or more to the ovaries (P = .002). The excess odds ratio per Gy was 0.36 for those who received ovarian doses less than 5 Gy and was 0.06 for those who received higher doses. Radiation-related risk did not vary significantly by age at exposure. Borderline significantly elevated risks were seen for doxorubicin, dactinomycin, dacarbazine, and carmustine.
Results confirm the radiation sensitivity of the breast in girls age 10 to 20 years but do not demonstrate a strong effect of age at exposure within this range. Irradiation of the ovaries at doses greater than 5 Gy seems to lessen the carcinogenic effects of breast irradiation, most likely by reducing exposure of radiation-damaged breast cells to stimulating effects of ovarian hormones.
Journal of Clinical Oncology 08/2009; 27(24):3901-7. · 18.37 Impact Factor
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ABSTRACT: There is some evidence that oxidative stress plays a role in lead-induced toxicity. Mechanisms for dealing with oxidative stress may be of particular relevance in the brain given the high rate of oxygen metabolism. Using a hospital-based case-control study, we investigated the role of oxidative stress in the potential carcinogenicity of lead through examination of effect modification of the association between occupational lead exposure and brain tumors by single nucleotide polymorphisms in genes with functions related to oxidative stress. The study included 362 patients with glioma (176 of which had glioblastoma multiforme), 134 patients with meningioma, and 494 controls. Lead exposure was estimated by expert review of detailed job history data for each participant. We evaluated effect modification with 142 single nucleotide polymorphisms using likelihood ratio tests that compared nested unconditional logistic regression models that did and did not include a cross-product term for cumulative lead exposure and genotype. When the analyses were restricted to cases with glioblastoma multiforme, RAC2 rs2239774 and two highly correlated GPX1 polymorphisms (rs1050450 and rs18006688) were found to significantly modify the association with lead exposure (P <or= 0.05) after adjustment for multiple comparisons. Furthermore, the same GPX1 polymorphisms and XDH rs7574920 were found to significantly modify the association between cumulative lead exposure and meningioma. Although the results of this study provide some evidence that lead may cause glioblastoma multiforme and meningioma through mechanisms related to oxidative damage, the results must be confirmed in other populations.
Cancer Epidemiology Biomarkers & Prevention 06/2009; 18(6):1841-8. · 4.12 Impact Factor
