3R Variant of Thymidylate Synthase 5’-untranslated Enhanced Region Contributes to Colorectal Cancer Risk: A Meta-analysis

Background: Studies investigating the association of 2R/3R polymorphism in the thymidylate synthase5’-untranslated enhanced region (TSER) and colorectal cancer (CRC) risk have reported conflicting results. Thus,a meta-analysis was performed to summarize the data on the potential association.
Methods: Pubmed, Embaseand CBM databases were searched for all available studies. Links between the TSER 2R/3R polymorphism andCRC risk were estimated by odds ratios (ORs) with 95% confidence intervals (CIs).
Results: Seven case-controlstudies with a total of 2723 cases and 4030 controls were included in this meta-analysis. The results showedthat the 3R variant of TSER 2R/3R polymorphism contributes to CRC risk in two comparison models (OR 3Rvs. 2R =1.10, 95%CI 1.02-1.18, P = 0.015; OR Homozygote comparison model = 1.22 1.04-1.43, 95%CI 1.04-1.43, P = 0.012). Subgroup analyses by ethnicity further demonstrated a contribution in Caucasians with threecomparison models (OR 3R vs. 2R = 1.10, 95%CI 1.02-1.19, P = 0.015; OR Homozygote comparison model =1.21, 95%CI 1.03-1.41, P = 0.019; OR Recessive comparison model = 1.18, 95%CI 1.05-1.33, P = 0.008). However,the association in the Asian population was still uncertain due to the limited data (all P values were more than0.05).
Conclusions: Our meta-analysis suggests that the 3R variant of Thymidylate synthase 5’-untranslatedenhanced region 2R/3R polymorphism contributes to gastric cancer risk in the Caucasian population, while anyassociation in Asian populations needs further study.