title: Polymorphisms in thymidylate synthase and methylenetetrahydrofolate reductase genes and the susceptibility to esophageal and stomach cancer with smoking.
abstract: Thymidylate synthetase (TS) and methylenetetrahydrofolate reductase (MTHFR) are major enzymes in the metabolism of folates, involved in DNA 'breaks', instability and hypomethylation. To investigate the possible relations between the TS 3'-UTR and MTHFR C677T polymorphisms and environmental factors impacting on risk of esophageal and stomach cancers, we conducted a case-control study in a high incidence region of China for these cancers. We recruited 138 esophageal and 155 stomach cancer cases, and 223 controls. The TS 3' -UTR and MTHFR C677T genotypes were detected by RFLP assay, using PCR products. The frequency of the -6 bp homozygous TS 3' -UTR genotype was 37.7 % in controls, higher than in Caucasians, although the present distribution was not in Hardy-Weinberg equilibrium. Ever-smoking with the -6 bp/-6 bp TS genotype elevated the ORs (2.61, 1.24-5.49; 3.54, 1.60-7.82) for cases of esophageal and stomach cancers, respectively, when compared with never-smoking with the +6 bp/+6 bp and +6 bp/-6 bp genotypes. No combination between the TS and MTHFR genotypes gave increased ORs. The present results suggest that TS polymorphism may modify the risk of esophageal and stomach cancer with smoking, pointing to the necessity for further investigations with information on folate and methionine intake with a larger population.
authors.affiliation: Department of Epidemiology, Jiangsu Province Institute of Cancer Research, Nanjing, China.
authors.forename: Chang-Ming
authors.initials: CM
authors.lastname: Gao
authors.forename: Toshiro
authors.initials: T
authors.lastname: Takezaki
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Wu
authors.forename: Yan-Ting
authors.initials: YT
authors.lastname: Liu
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Ding
authors.forename: Su-Ping
authors.initials: SP
authors.lastname: Li
authors.forename: Ping
authors.initials: P
authors.lastname: Su
authors.forename: Xu
authors.initials: X
authors.lastname: Hu
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Kai
authors.forename: Zong-You
authors.initials: ZY
authors.lastname: Li
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hamajima
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sugimura
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tajima
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D015331:Cohort Studies; D004938:Esophageal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011336:Probability; D012307:Risk Factors; D017678:Sex Distribution; D012907:Smoking / Q000453:epidemiology; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016019:Survival Analysis; D013940:Thymidylate Synthase / Q000235:genetics*
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013940:Thymidylate Synthase