title: Polymorphisms in the thymidylate synthase gene and risk of colorectal cancer.
abstract: To evaluate the relationship between polymorphisms (28 bp repeated sequences in 5'-UTR and 6-bp ins/ del in 3'-UTR) in then thymidylate synthetase gene (TS) and risk of colorectal, colon and rectal cancers, we conducted a case-control study with 315 cases of colorectal cancer and 439 population-based controls in Jiangsu province, China. TS genotypes were identified using PCR-RFLP (restriction fragment length polymorphism) methods. Odds ratios (ORs) were estimated with an unconditional logistic regression model. We found that the distributions of 5'-UTR genotypes in TS were significantly different between controls and male colon cases (χ2 =8.25, P = 0.016). Compared with 3R/3R genotype, individuals with the 2R allele were at an increased risk of colon cancer (age-, BMI-, smoking- and alcohol drinking-adjusted OR=1.98, 95%CI: 1.11-3.53) among men. In contrast, the 6-bp ins/del polymorphism at the TS 3'- UTR did not influence risk of the colorectal, colon and rectal cancers. When combined genotypes for both TS 5'-UTR and 3'-UTR polymorphisms were evaluated, individuals with the 5'-UTR 2R allele had a OR of 3.61 (95%CI: 1.38-9.49) for colon cancer among men with the 3'-UTR -6bp/-6bp genotype. These results show that the polymorphism of the 28 bp repeated sequences in TS 5'-UTR could influence susceptibility to colon cancer and that there was a coordinated effect between TS 3'-UTR and 5'-UTR polymorphisms in increasing risk of colon cancer among Chinese men.
authors.affiliation: Department of Epidemiology, Jiangsu Province Institute of Cancer Research, Nanjing, China. gaocm888@126.com
authors.forename: Chang-Ming
authors.initials: CM
authors.lastname: Gao
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Ding
authors.forename: Su-Ping
authors.initials: SP
authors.lastname: Li
authors.forename: Yan-Ting
authors.initials: YT
authors.lastname: Liu
authors.forename: Hai-Xia
authors.initials: HX
authors.lastname: Cao
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Wu
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tajima
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D020121:5' Untranslated Regions / Q000235:genetics*; D016022:Case-Control Studies; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000209:etiology*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis; D012007:Rectum / Q000378:metabolism; D012307:Risk Factors; D013940:Thymidylate Synthase / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D013940:Thymidylate Synthase