Association between polymorphic sites in thymidylate synthase gene and risk of non-Hodgkin lymphoma: a systematic review and pooled analysis.

Epidemiological studies have evaluated the association between polymorphic sites in the thymidylate synthase (TYMS) gene and non-Hodgkin lymphoma (NHL) risk, but the results remain controversial. Here we performed a meta-analysis to estimate the relationship between TYMS polymorphisms and the risk of NHL and two of its subtypes from all nine published case-control studies. Our meta-analysis suggested that both 1053C > T and IVS6-68C >T polymorphisms were significantly associated with decreased risks of NHL among Caucasians (for 1053C > T: TT vs. CC, odds ratio [OR] = 0.78, 95% confidence interval [CI] = 0.64-0.95; recessive model, OR = 0.81, 95% CI = 0.67-0.98 and for IVS6 - 68C > T: TT vs. CC, OR = 0.61, 95% CI = 0.40-0.92; recessive model, OR = 0.63, 95% CI = 0.42-0.93), whereas the TSER, 1122A > G and 1494del6 polymorphisms had no influence on the susceptibility to NHL. Further analysis revealed that the T allele of the 1053C > T polymorphism might provide protective effects in Caucasians against the risk of NHL (OR = 0.90, 95% CI = 0.82-0.98) and follicular lymphoma (FL) (OR = 0.81, 95% CI = 0.71-0.93), but not diffuse large B-cell lymphoma (DLBCL). Additionally, the IVS6 - 68C > T variant homozygote genotype was significantly associated with reduced risks for DLBCL (TT vs. CC: OR = 0.51, 95% CI = 0.28-0.94; recessive model: OR = 0.53, 95% CI = 0.29-0.96), but not FL. However, individuals carrying the T allele of the IVS6 - 68C > T polymorphism were not significantly associated with reduced risks for DLBCL and FL.