The association between two polymorphisms in the TS gene and risk of cancer: A systematic review and pooled analysis
A partir d'une revue systématique de la littérature (63 études sur le polymorphisme TSER avec 19 707 cas et 27 398 témoins, 39 études sur le polymorphisme TS1494del6 avec 13 489 cas et 16 297 témoins), cette synthèse analyse l'association entre deux polymorphismes du gène TS et le risque de cancer
Thymidylate synthase (TS) is an important enzyme involved in folate metabolism and catalyzes methylation of dUMP to dTMP, which is essential for DNA replication. TSER and TS1494del6, two functionally important and ethnically diverse polymorphisms mapping to its gene region, are the most extensively studied. Considering the potential influence of altering TS activity, it is plausible that TS polymorphisms might play a role in the development of cancer. Although the effects of TS polymorphisms on susceptibility to human cancer have been investigated in many studies, the results remain conflicting rather than conclusive. In order to resolve these conflicts, we performed a quantitative synthesis of the evidence on the association between these two polymorphisms and cancer risk, including 63 studies (19,707 cases and 27,398 controls) for TSER polymorphism and 39 studies (13,489 cases and 16,297 controls) for TS1494del6 polymorphism. Our meta-analysis suggested that these two polymorphisms are not associated with cancer risk when all studies were pooled together. In the stratified analyses, we found that individuals with 2R/2R genotype had a significantly higher cancer risks among Asians (2R/2R vs. 3R/3R: OR=1.24, 95% CI=1.05–1.45; recessive model: OR=1.23, 95%CI=1.05–1.44). Further analyses revealed that 2R/2R genotype was significantly associated with an increased risk of gastroesophageal cancer among Asians, whereas it might provide protecting effects against colorectal cancer risk in a dominant genetic model for Caucasians. Additionally, TS1494del6 polymorphism may contribute to genetic susceptibility of breast cancer among Asians. © 2012 Wiley-Liss, Inc.