Alcohol drinking and one-carbon metabolism-related gene polymorphisms on pancreatic cancer risk
Alcohol drinking and one-carbon metabolism-related gene polymorphisms on pancreatic cancer risk
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DOI：
10.1158/1055-9965.epi-08-0470
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发表时间：
2008-10-01
影响因子：
3.8
通讯作者：
Tanaka, Hideo
中科院分区：
文献类型：
--
作者：
Suzuki, Takeshi;Matsuo, Keitaro;Tanaka, Hideo
饮酒对胰腺癌风险的影响已经在许多研究中进行了研究，但结果并不一致。我们进行了一项病例对照研究，以评估酒精对胰腺癌的影响与一碳代谢酶，亚甲基四氢叶酸还原酶（MTHFR C677 T），甲硫氨酸合成酶（MTR A2756 G），甲硫氨酸合成酶还原酶（MTRR A66 G）和胸苷酸合成酶（TS）可变串联重复数的多态性。共有157名胰腺癌患者和785名年龄和性别匹配的对照组进行了多态性基因分型。采用校正潜在混杂因素的无条件logistic模型估计比值比（OR）和95%置信区间（95% CD）。重度饮酒与胰腺癌风险增加略有相关（OR，1.90; 95%CI，1.00-3.62）。没有一个多态性单独对基因型的胰腺癌风险有显著影响。在分层分析中，在携带MTHFR 667 CC、MTR 2756 AA或MTRR 66 G等位基因的个体中观察到饮酒对胰腺癌的影响。MTHFR 667 CC基因型、MTR 2756 AA基因型和MTRR 66 G等位基因携带者患胰腺癌的OR（95% CI）分别为4.50（1.44-14.05）、2.65（1.17-6.00）和3.35（1.34-8.36）。这些结果表明，叶酸相关酶多态性改变饮酒习惯和胰腺癌风险之间的关联。
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% CD 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.