Chernobyl Papillary Thyroid Carcinoma Reveals a Complex Interplay between Environmental Exposures and Lead Genetic Variants Predisposing to Thyroid Cancer

Environmental exposures to radioactive and stable iodine and predisposing germline genetic variants contribute to the development of papillary thyroid carcinoma (PTC) after the Chernobyl accident, but their joint effects and interaction effects remain unknown. A retrospective observational case-control study enrolled 945 PTC patients and 1040 healthy control individuals from Belarus aged 0–18 years old at the time of exposure. Clinicopathological data, individual radiation doses to the thyroid, extent of stable iodine consumption, and genotypes for six predisposing genetic variants were used in the multiplicative and additive statistical models to address the individual environmental (E) and genetic factor (G) effects, and those of E×E, G×G, and G×E interactions. The radiation dose and soil iodine level were statistically significantly associated with PTC and displayed a negative interaction. Out of six, four genetic variants displayed significant association signals with a positive interaction between two of them. Importantly, one of these variants negatively interacts with the radiation dose. The soil iodine level did not interact with genetic components. The impact of radiation exposure was stronger than that of genetic variants. The findings show that environmental and genetic factors demonstrate complex nonindependent effects on the development of thyroid cancer after childhood radiation exposure and point at the absence of radiation risk augmentation by the major cancer-associated genetic variants. These observations can be used for radiation risk communication with the public.