Abstract: Objective To study the relationship between the polymorphism in the 5'-untranslated region(5'-UTR) of thymidylate synthase(TS) gene and the susceptibility of lung cancer.Methods We conducted a case-control study with 473 lung cancer patients and 641 healthy controls in Qingdao population.The TS 5'-UTR tandem repeat genotype was analyzed with polymerase chain reaction.Unconditional logistic regression was used to analyze the relationship between TS 5'-UTR polymorphism and lung cancer susceptibility.Results The frequency of TS 5 '-UTR genotypes(3R/3R,2R/3R,2R/2R) was 62.2%,34.0%,and 38% in the lung cancer patients and 60.5%,37.0%,and 2.5% in the controls,respectively.Compared with TS 5'-UTR 3R/3R genotype,2R/3R genotype showed a decreased risk of lung cancer(odds ratioOR=0.90,95%confidence intervalCI:0.69-1.17),while 2R/2R genotype showed an increased risk(OR=1.64,95% CI:0.80-3.38).However,the results did not reach statistical significance(P > 0.05).After adjusting for age,gender,smoking,alcohol use,and histological type and stage,no significant effect of the TS 5'-UTR polymorphism was found in each subgroup.Conclusion There was no evidence for a major role of the polymorphism of TS 5'-UTR in carcinogenesis of lung cancer by genotype alone and no obvious interaction was found between smoking,alcohol use and the polymorphism in lung cancer development.