title: Thymidylate synthase polymorphisms and hematological cancer risk: a meta-analysis.
abstract: 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.
authors.affiliation: Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Weng
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Xue
authors.initials: X
authors.lastname: Tang
authors.forename: Xinyou
authors.initials: X
authors.lastname: Xie
authors.forename: Guangdi
authors.initials: G
authors.lastname: Chen
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D020121:5' Untranslated Regions / Q000235:genetics; D000328:Adult; D044466:Asian People / Q000235:genetics; D002648:Child; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D019337:Hematologic Neoplasms / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000208:ethnology / Q000235:genetics; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000208:ethnology / Q000235:genetics; D012307:Risk Factors; D013940:Thymidylate Synthase / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D013940:Thymidylate Synthase