Thymidylate synthase genetic polymorphisms and cancer risk: a meta-analysis of 37 case-control studies

Background Several studies have evaluated the association between polymorphisms of thymidylate synthase (TS) and cancer risk in diverse populations but with conflicting results. By pooling the relatively small samples in each study, it is possible to evaluate the association using a meta-analysis. Methods A comprehensive search was conducted to identify all case-control studies on TS on a 28-bp tandem repeats in 5'untranslated region (5'UTR) and a 6-bp insertion (ins) and deletion (del) mutation in 3'UTR of the gene and cancer risk. Meta-analysis was conducted using a fixed and random effect model. Results Our meta-analysis on a total of 13 307 cancer cases and 18 226 control subjects from 37 published case-control studies showed no significant association between the risk of cancer and the 5'UTR 28-bp tandem repeats polymorphism (3R/3R vs. 2R/2R: OR=1.06, 95% CI, 0.93-1.20) or the 3'UTR 6-bp ins/del polymorphism (del6/del6 vs. ins6/ins6: OR=0.93, 95% CI, 0.81-1.08) with significant between-study heterogeneity. In the cancer type- and ethnic subgroup-stratification analyses, we did not find any association between TS polymorphisms and cancer risk either. Conclusion TS 5'UTR 28-bp tandem repeats and 3'UTR 6-bp ins/del polymorphisms may not be associated with cancer risk. Chin Med J 2012;125(14):2582-2588