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风险的原因之一。这项研究的目的是在全基因组水平上分析测量个体遗传变异(G)与环境因素(E)如辐射、碘和硝酸盐的相互作用(因此，GxE相互作用)对切尔诺贝利受影响地区甲状腺恶性肿瘤风险的影响。我们先前对切尔诺贝利事故后发生的甲状腺癌患者和白俄罗斯健康对照组进行的全基因组研究只考虑了人口统计学信息，即采用生态设计。在本研究中，关于个人辐射甲状腺剂量的数据，这项研究是由基因组分析、医学肿瘤学和病理学、环境和辐射剂量学等不同知识领域的专家进行的一项国际跨学科合作研究。来自GxE相互作用的知识预计将为基于科学证据的风险交流和在世界范围内不断增加的医疗照射和意外辐射暴露或技术辐射灾难条件下的个人风险管理提供基本数据。

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.