Folic Acid Metabolism Key Enzymes TYMS, MTHFR Gene Polymorphism And Susceptibility To Lung Cancer In Han Population In East China

Folic acid metabolism is an important biochemical reaction in human bodies, which has relations to DNA synthesis and the methylation of DNA, RNA, protein, lipid, and so on. Folic acid metabolic imbalance will lead to the disorder of biochemical reactions in vivo, which will cause cardiovascular disease, neural tube malformation, immunodeficiency, tumor and other complex diseases. TYMS and MTHFR are two key enzymes in folic acid metabolic pathway. TYMS catalyses the only reaction of dTMP synthesis in vivo, and MTHFR is the speed limits enzyme of intracellular methylation reactions.We evaluated the SNP rs3819102in TYMS3’flanking region, and rs1801133, also known as MTHFR C677T, rs17037396of MTHFR in association with lung cancer susceptibility in a population-based case-control study of974incident lung cancer cases and1,005sex, age matched population controls. Epidemiological information was obtained through face to face interview, and the gene-environment, gene-gene interaction are also evaluated.We found that the lung cancer risk was statistically significantly associated with rs3819102(P=0.018) in the single locus analysis. Both heterozygote and mutant homozygote are risk factors after logistic regression analysis. The risky effects of rs3819102were evident in different ages and smoking status, and more evident in males, adenocarcinoma and squamous cell carcinoma patients.Rs1801133, a C677T variant of MTHFR, was found significantly different between patients and control subjects (P=0.0001). Further logistic regression analysis revealed that the heterozygote CT was associated with decreased risk of developing lung cancer (OR=0.08,95%CI=0.64-0.99, P=0.045). This effect was more observed in males.Another SNP rs17037396of MTHFR was not significantly different between cases and controls. But further logistic regression analysis revealed that the mutant homozygote AA were associated with a risky effect of developing lung cancer (OR=3.30,95%CI=1.32-8.27, P=0.011).Haplotype analysis revealed that the rs1801133variant allele T and rs17037396allele G has a joint effect of reducing lung cancer risk (OR=0.86,95%CI=0.75-0.99, P=0.038). No gene-gene interaction between TYMS and MTHFR was found to be related to lung cancer susceptibility in this study.