Polymorphism rs3819102 in thymidylate synthase and environmental factors: effects on lung cancer in Chinese population

Purpose: Lung cancer is the leading cause of cancer death worldwide, and the predominant risk factor for its development is smoking. Thymidylate synthase (TYMS) is a key enzyme in DNA synthesis that catalyzes the conversion of deoxyuridine monophosphate to dTMP. Rs931794, a single nucleotide polymorphism located in the TYMS gene, was suggested to be associated with cancer risk. Methods: To analyze the interaction between rs3819102 and environmental factors on the risk of lung cancer in a Chinese population, single nucleotide polymorphismscan was used to genotype this polymorphism in 974 lung cancer cases and 1005 control subjects. Results: The frequencies of TT, CT, and CC genotypes of TYMS rs3819102 were 61.8%, 32.9%, and 5.3% in controls, and 53.8%, 38.4%, and 7.8% in cases, respectively. Compared with the TT genotype, the CT (odds ratio [OR], 1.380; 95% confidence interval [CI], 1.131-1.683), and CC (OR, 1.786; 95% CI, 1.2132.644) genotypes were associated with an increased risk of lung cancer after adjustment for age, gender, smoking status, and family history. The C allele of rs3819102 is the risk allele for lung carcinogenesis in a dominant model (OR, 1.435; 95% CI, 1.188-1.735). In a stratified analysis, the risk effects of both the CT and CC genotypes of rs3819102 were more evident in subgroups of smokers and people without a family history of cancer. Conclusion: The rs3819102 polymorphism in TYMS might increase susceptibility to environmental factors and contribute to the risk of lung cancer. The C allele is a risk allele in lung carcinogenesis. (C) 2018 Elsevier Inc. All rights reserved.