Smoking, Genetic Polymorphisms In Dna Repair Genes And Risk Of Thyroid Cancer

While the number of current smokers has declined due to legal and regulatory measures and public health awareness, cigarette smoking remains the top risk factor for many diseases, including cancers originated from various tissues. Meanwhile, thyroid cancer incidence has increased significantly in the USA. Former epidemiology studies have investigated the association between smoking and risk of thyroid cancer, and interestingly results from these studies have shown that smoking has protective effect on risk of thyroid cancer. Studies have tapped into genetic polymorphisms and their association with thyroid cancer (and its subtypes) to further examine the susceptibility of certain gene variants carriers, and these studies have covered multiple SNPs of genes, which belong to relevant pathways including xenobiotic metabolism, DNA damage response and repair. Neither did the results from these studies form a consistent opinion about which SNPs/genes/pathways are associated with thyroid cancer among specific population, nor did they give confirmed explanation about molecular mechanisms supporting their results. In the current study, we investigated the association between smoking and thyroid cancer with stratification for 299 SNPs of 340 DNA repair genes. Study subjects included 440 cases diagnosed between 2010 and 2011 from Yale Cancer Center’s Rapid Case Ascertainment Shared Resource, and 465 pairing controls in Connecticut. The study was conducted to test the hypothesis that genetic variations in DNA repair genes modify the association between smoking and risk of thyroid cancer. RPA1 (replication protein A1 gene) rs11867830 have shown statistically significant effect modification for smoking-papillary thyroid cancer association. ALKBH3 (alkB homolog 3, alpha-ketoglutarate-dependent dioxygenase gene) rs10768995 and rs197371 significantly modified such association for follicular thyroid cancer subtypes. MAD2L2 (MAD2 mitotic arrest deficient-like 2 gene) rs747863, RAD54L (RAD54-like (S. cerevisiae) gene) rs10789488, TDG (thymine DNA glycosylase gene) rs2700505, rs322106, and rs322107 are demonstrated to have significant effect modification for overall cases of thyroid cancer