Alcohol drinking and one-carbon metabolism-related gene polymorphisms on pancreatic cancer risk.
Effect of alcohol consumption on pancreatic cancer risk has been investigated in many studies, but results have been inconsistent. We conducted a case-control study to assess the effect of alcohol on pancreatic cancer in conjunction with polymorphisms in one-carbon metabolism enzymes, methylenetetrahydrofolate reductase (MTHFR C677T), methionine synthase (MTR A2756G), methionine synthase reductase (MTRR A66G), and thymidylate synthase (TS) variable number of tandem repeat. A total of 157 pancreatic cancer patients and 785 age- and sex- matched control subjects were genotyped for polymorphisms. Odds ratios (OR) with 95% confidence intervals (95% CI) were estimated using unconditional logistic models adjusted for potential confounders. Heavy alcohol drinking was marginally associated with an increased risk of pancreatic cancer (OR, 1.90; 95% CI, 1.00-3.62). None of the polymorphisms showed any significant effect on pancreatic cancer risk by genotype alone. In stratified analysis, effect of alcohol consumption on pancreatic cancer was observed in individuals with the MTHFR 667 CC, MTR 2756 AA, or MTRR 66 G allele. OR (95% CI) of pancreatic cancer for heavy drinkers compared with never drinkers was 4.50 (1.44-14.05) in the MTHFR 667 CC genotype, 2.65 (1.17-6.00) in the MTR 2756 AA genotype, and 3.35 (1.34-8.36) in the MTRR 66 G allele carriers. These results suggest that the folate-related enzyme polymorphism modifies the association between drinking habit and pancreatic cancer risk.
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan. t_suzuki@aichi-cc.jp
Takeshi
T
Suzuki
Keitaro
K
Matsuo
Akira
A
Sawaki
Nobumasa
N
Mizuno
Akio
A
Hiraki
Takakazu
T
Kawase
Miki
M
Watanabe
Tsuneya
T
Nakamura
Kenji
K
Yamao
Kazuo
K
Tajima
Hideo
H
Tanaka
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects* / Q000235:genetics; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics* / Q000378:metabolism; D005838:Genotype; D006801:Humans; D007564:Japan; D016015:Logistic Models; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000235:genetics*; D011110:Polymorphism, Genetic; D012306:Risk; D013940:Thymidylate Synthase / Q000235:genetics / Q000378:metabolism
C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D013940:Thymidylate Synthase