Polymorphisms in thymidylate synthase and methylenetetrahydrofolate reductase genes and the susceptibility to esophageal and stomach cancer with smoking.
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.
Gao
Chang-Ming
CM
Department of Epidemiology, Jiangsu Province Institute of Cancer Research, Nanjing, China.
Takezaki
Toshiro
T
Wu
Jian-Zhong
JZ
Liu
Yan-Ting
YT
Ding
Jian-Hua
JH
Li
Su-Ping
SP
Su
Ping
P
Hu
Xu
X
Kai
Hai-Tao
HT
Li
Zong-You
ZY
Matsuo
Keitaro
K
Hamajima
Nobuyuki
N
Sugimura
Haruhiko
H
Tajima
Kazuo
K
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*
D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013940:Thymidylate Synthase