Thymidylate synthase polymorphisms and hematological cancer risk: a meta-analysis

Previous studies on the association of Thymidylate synthase (TYMS) polymorphisms with risk of hematological malignancies have produced conflicting results. The purpose of this meta-analysis was to define the effect of TYMS 5'-untranslated enhanced region (TSER) and 3'-untranslated region (TS3'-UTR) polymorphisms on the risk of hematological malignancies. Seventeen articles were identified as eligible in the case of TSER (2R > 3R) polymorphism (4511 cases and 6113 controls) and seven articles in the case of TS3'-UTR (1494del6) polymorphism (2721 cases and 3761 controls). The overall results suggested that either TSER or TS3'-UTR polymorphism was not associated with the risk of hematological malignancies. In stratified analyses, significantly decreased acute lymphoblastic leukemia (ALL) risk was found in adults (2R/3R vs. 2R/2R: odds ratio [OR] = 0.64, 95% confidence interval [CI]: 0.43-0.97), but increased ALL risk was observed in children (3R/3R vs. 2R/2R: OR = 1.46, 95% CI: 1.03-2.06). Increased non-Hodgkin lymphoma risk was found in the Caucasian population (2R/3R vs. 2R/2R: OR = 1.31, 95% CI: 1.10-1.56). Protective effects of the TS3'-UTR polymorphism (-6 bp/-6 bp) on hematological malignancies were found in a homozygote model and recessive model when the source of controls was stratified as hospital based. In conclusion, the TYMS TSER polymorphism may contribute to a susceptibility to risk of ALL in children and non-Hodgkin lymphoma in Caucasians, but protection from ALL risk in adults. The TS3'-UTR polymorphism (-6 bp/-6 bp) may have a protective effect in hematological malignancies.