Genome-wide gene-environmental interaction analysis of exposures to radiation and nitrates as modifiers of the risk for thyroid cancer in the Chernobyl region

遗传和环境因素被认为是导致甲状腺癌发展的风险。本研究的目的是在全基因组尺度上分析测量个体遗传变异（G）与环境因素（E）（如辐射、碘和硝酸盐）相互作用的影响（因此，GxE相互作用）对受辐射影响地区甲状腺恶性肿瘤风险的影响。我们以前对辐射遗传易感性的全基因组研究-在切尔诺贝利事故后发展的甲状腺癌患者组和来自白俄罗斯的健康对照个体中进行了相关的甲状腺癌发生，仅考虑人口统计学信息，即使用生态设计。关于个人甲状腺辐射剂量的数据，研究参与者在暴露时居住地土壤中的碘水平和饮用水中的硝酸盐浓度正在生成，并与综合统计和机器学习模型中的现有基因组数据相结合。这项研究是一项国际跨学科合作研究，不同的知识领域，如基因组分析，医学肿瘤学和病理学，环境和辐射剂量学。GxE相互作用的知识有望在全球医疗照射增加、意外辐射照射或技术性辐射灾害的条件下，为基于科学证据的风险沟通和个人风险管理提供必要数据。

Genetic and environmental factors are thought to contribute to the risk of development of thyroid cancer. The purpose of this study is to analytically measure on the whole-genome scale the impact of interactions of individual genetic variants (G) with environmental factors (E) such as radiation, iodine and nitrates (hence, GxE interactions) on the risk for thyroid malignancy in the Chernobyl-affected region.Our previous whole-genome study of genetic predisposition to radiation-related thyroid carcinogenesis was performed in the groups of patients with thyroid cancer developed after the Chernobyl accident and healthy control individuals from Belarus taking into account only demographic information, i.e. using an ecological design.In the present study, data on individual radiation thyroid dose, and iodine level in soil and nitrate concentration in drinking water in the place of residence of study participants at the time of exposure are being generated and integrated with the available genomic data in comprehensive statistical and machine learning models.This study is an international interdisciplinary collaborative research conducted by the specialists in different areas of knowledge such as genome analysis, medical oncology and pathology, environment, and radiation dosimetry. Knowledge from GxE interactions is expected to provide essential data for scientific evidence-based risk communications and individual risk management under the conditions of increasing medical exposures worldwide, and accidental radiation exposure or technogenic radiation disaster.