Studies of Populations Exposed to Environmental Sources of Radiation

1986年发生在乌克兰的切尔诺贝利核反应堆事故污染了白俄罗斯、乌克兰西北部和与俄罗斯接壤省份的大部分地区。在白俄罗斯进行的一项病例对照研究，根据个人剂量估计，表明甲状腺癌与与切尔诺贝利事故有关的沉降物产生的环境辐射剂量之间存在统计学上显著的联系。研究中心及其合作者组织了对白俄罗斯和乌克兰切尔诺贝利事故放射性尘降物的儿童的良性和恶性甲状腺疾病的后续筛查研究。每两年对每个国家约12 000名受试者的甲状腺进行筛查，乌克兰为4个周期，白俄罗斯为3个周期。这些项目目前正准备利用现有的国家癌症登记处从主动筛查过渡到其他形式的随访。俄罗斯马亚克核设施排放到捷查河的放射性废物暴露人群中的癌症死亡率生活在俄罗斯捷查河沿岸的村民受到马亚克核设施排放到捷查河的放射性废物的慢性外部和内部环境辐射。正在对大约3万名从受污染的河流中接受低至中等剂量辐射的人进行癌症死亡率评估。目前的工作重点是提高数据质量，追踪人口的重要状态信息，以及统计分析和手稿准备。已经观察到实体癌和白血病死亡率与辐射剂量之间的关系。我们发起了一项基于队列的神经胶质瘤全基因组关联研究，包括来自队列联盟的18项研究，目的是确认与神经胶质瘤风险相关的基因区域，确定在队列设置中可能更明显的遗传易感性的新区域，并根据队列中可用的协变量数据进行靶向基因环境分析。为了研究乳腺癌幸存者患第二种癌症的风险，我们正在评估AARP队列中乳腺癌诊断后的行为变化（如吸烟和饮酒）。然后，我们计划评估这些可改变的危险因素与肥胖以及这些妇女患对侧乳腺癌的风险之间的关系。NHANES III：前瞻性维生素研究NHANES III数据集测量了大约20,000人的维生素D水平，这是一个独特的资源，可以调查维生素D与特定死亡原因之间的关系。这个队列包括实际的维生素D测量和大约2253例死亡，其中近900例是癌症死亡。我们之前发表了一项关于2000年基线维生素D与所有癌症死亡率之间关系的研究，该研究发现与癌症死亡率没有关联，包括癌症部位和亚组。通过评估额外随访期的风险，到2006年，我们发现维生素D与癌症死亡率没有关联，但一些亚组和结果显示出不利的关联。来自NCI成人脑肿瘤研究的北欧脑协作分析已经确定了脑肿瘤的可能危险因素，包括环境因素，如暴露于铅，以及遗传因素，包括涉及铅代谢的多态性。我们计划使用北欧成人脑肿瘤病例对照研究的数据来验证这些假设，以进行重复性研究。最近发表的神经胶质瘤全基因组关联研究表明，编码端粒酶逆转录酶（一种对维持端粒长度至关重要的酶）的TERT基因可能在神经胶质瘤的病因学中起重要作用。我们建议研究端粒长度与胶质瘤风险之间的关系，并将探索端粒长度变化是否受到与胶质瘤风险高度相关的TERT多态性的修饰。甲状腺癌遗传联盟（THYGENE）：我们计划对分化甲状腺癌进行GWAS（全基因组关联研究），使用来自THYGENE（包括USRT）的几项研究中的4,000例病例和来自其他大型研究对照系列的10,000例对照，并在1500例甲状腺癌病例和其余THYGENE联盟成员的对照中进行复制。这些研究包括受辐射和未受辐射的受试者。在塞米巴拉金斯克核试验场儿童时期受核辐射尘降物影响的3000名哈萨克斯坦居民中，甲状腺结节作为辐射风险的衡量指标作为主要结果变量，用于评价1949-1962年期间在附近塞米巴拉金斯克试验场进行的核弹试验产生的放射性沉降物对哈萨克斯坦3000名村庄居民的环境辐射沉降物暴露的影响。NCI和莫斯科生物物理研究所联合开发了一种新的剂量重建算法，主要基于居住史和在受污染牧场放牧的奶牛的估计牛奶消费量，用于估计来自外部和内部放射性尘降源的个体甲状腺剂量。发现外用和内用剂量均与结节患病率显著且独立相关。目前的工作重点是剂量不确定性的来源，特别是那些涉及通过从牧场到牛奶的食物链摄入的碘的放射性同位素的内部剂量。研究了13个基因的多态变异对辐射剂量-反应关系的影响及其对甲状腺结节发病的主要影响。发现XRCCI变异与辐射剂量和甲状腺结节风险相互作用。紫外线照射、电离辐射和皮肤及其他癌症的风险暴露于阳光中的紫外线（UV）辐射在黑色素瘤和非黑色素瘤皮肤癌的病因学中起着主要作用，但两者之间关系的本质是复杂的，尚未完全了解。特别是，暴露于电离辐射可能产生的相互作用尚不清楚。我们最近完成了来自7万多名美国放射技术人员的终身紫外线辐射相关暴露的问卷收集，并进行了分析，以评估与这种暴露相关的特定形式癌症的风险。我们还计划评估与电离辐射职业暴露相关的皮肤癌风险是否可以通过问卷得出的紫外线相关辐射暴露估计值进行修正。我们已经开始分析一生中自我报告的户外活动时间与预期诊断的结直肠腺瘤之间的关系数据。

Benign and Malignant Thyroid Disease Among Those Exposed as Children to Fallout from the Chornobyl Accident The Chernobyl nuclear reactor accident in Ukraine in 1986 contaminated large parts of Belarus, northwestern Ukraine, and bordering Russian provinces. A case-control study in Belarus, with individual dose estimates, demonstrated a statistically significant link between thyroid cancer and environmental radiation dose from fallout related to the Chornobyl accident. REB and collaborators organized follow-up screening studies of benign and malignant thyroid disease among those exposed as children to fallout from the Chornobyl accident in Belarus and in Ukraine. The thyroid glands of approximately 12,000 subjects in each country have been screened biennially for four cycles in Ukraine and three cycles in Belarus. The projects are currently preparing to transition from active screening to other forms of follow-up using the existing national cancer registries. Cancer Mortality Among the Population Exposed to Radioactive Waste Released in to the Techa River by the Mayak Nuclear Facility in Russia Villagers living along the banks of the Techa River in Russia were exposed to chronic external and internal environmental radiation from radioactive waste released into the river by the Mayak nuclear facility. Cancer mortality is being evaluated in a cohort of approximately 30,000 people who received low to moderate radiation doses from the contaminated river. Current efforts focus on improving data quality, tracing the population for vital status information, and on statistical analyses and manuscript preparation. Associations between solid cancer and leukemia mortality and radiation dose have been observed. Cohort-based GWAS of Glioma We have initiated a cohort-based genome wide association study of glioma including 18 studies from the Cohort Consortium, with the aim of confirming gene regions associated with glioma risk, identifying new regions of genetic susceptibility that might be more apparent in a cohort setting, and conducting targeted gene-environment analyses based on the covariate data available from the cohorts. Contralateral Breast Cancer in AARP To study the risks for second cancers in breast cancer survivors we are evaluating changes in behavior after breast cancer diagnosis (such as smoking and alcohol consumption) in the AARP cohort. We then plan to evaluate the association between these modifiable risk factors and obesity and the risk of developing a contralateral breast cancer in these women. NHANES III: Prospective Vitamin Study The NHANES III data set with measured vitamin D levels on about 20,000 people is a unique resource that allows investigation of the relationship between vitamin D and specific causes of mortality. This cohort includes actual vitamin D measurements and about 2253 deaths, of which nearly 900 are cancer deaths. We previously published a study on the relationship between baseline vitamin D and all cancer mortality as of 2000, which found no association with cancer mortality, including by cancer site and within subgroups. Assessing risks accounting for an additional follow-up period, through 2006 we found no association of Vitamin D with cancer mortality, but some subgroups and outcomes showed adverse associations. Nordic Brain Collaboration Analyses from the NCI Adult Brain Tumor Study have identified possible risk factors for brain tumors including environmental factors such as exposure to lead, and genetic factors, including polymorphisms involved in lead metabolism. We plan to test these hypotheses using data from Nordic case-control studies of adult brain tumors for replication studies. Telomere Length and Risk of Glioma Recently published genome wide association studies of glioma indicate that the TERT gene, which codes for telomerase reverse transcriptase (an enzyme crucial to the maintenance of telomere length), is likely to be important in glioma etiology. We propose to examine the association between telomere length and the risk of glioma, , and will explore whether telomere length variation is modified by TERT polymorphisms that are highly associated with glioma risk. Thyroid Cancer Genetic Consortium (THYGENE) We are planning to perform a GWAS (Genome-Wide Association Studies) of differentiated thyroid cancer using 4,000 cases from several studies in THYGENE (including USRT) and 10,000 controls amassed from control series of other large studies, with replication in 1500 thyroid cancer cases and controls by remaining THYGENE consortium members. These studies include radiation- and non-radiation-exposed subjects. Thyroid Nodules as a Measure of Radiation Risk Among a Population of 3000 Residents in Kazakhstan Exposed as Children to Fallout from Nuclear Testing at the Semipalatinsk Test Site Thyroid nodule prevalence, determined by ultrasound screening, was used as the main outcome variable for evaluating the effects of environmental radiation fallout exposure in a population of 3000 village residents in Kazakhstan affected by radioactive fallout from nuclear bomb tests at the nearby Semipalatinsk Test Site during 1949-1962. A new dose-reconstruction algorithm, developed jointly by NCI and the Institute of Biophysics in Moscow, was used to estimate individual thyroid doses from external and internal sources of fallout-derived radiation, based mainly upon residential history and estimated consumption of milk from dairy animals grazing on contaminated pasture. Both external and internal dose were found to be significantly and independently associated with nodule prevalence. Current efforts, are focused on sources of dose uncertainty, especially those involving internal dose from radioactive isotopes of iodine ingested through the pasture-to-milk food chain. Polymorphic variants in 13 genes were studied for effect modification of the radiation dose-response relation and main effects on thyroid nodule risk. A variant in XRCCI was found to interact with radiation dose and thyroid nodule risk. Ultraviolet Sunlight Exposure, Ionizing Radiation, and Risk of Skin and Other Cancers Exposure to ultraviolet (UV) radiation from sunlight plays a predominant role in the etiology of melanoma and non-melanoma skin cancer, but the nature of the relationship is complex and not fully understood. In particular, the possible interaction with exposure to ionizing radiation is unclear. We recently completed questionnaire-based collection of lifetime UV sun-related radiation exposure from more than 70,000 U.S. radiologic technologists and have undertaken analyses to assess risks of specific forms of cancer in relation to this exposure. We also plan to evaluate whether skin cancer risks associated with occupational exposures to ionizing radiation might be modified by questionnaire-derived estimates of UV sun-related radiation exposures. UV exposure and Colorectal adenomas in the Fernald Community cohort We have begun to analyze data on the relationship between self-reported time outdoors throughout life and prospectively diagnosed colorectal adenomas.