Alcohol dehydrogenase and aldehyde dehydrogenase polymorphisms and colorectal cancer:: The Fukuoka Colorectal Cancer Study
Alcohol dehydrogenase and aldehyde dehydrogenase polymorphisms and colorectal cancer:: The Fukuoka Colorectal Cancer Study
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DOI：
10.1111/j.1349-7006.2007.00519.x
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发表时间：
2007-08-01
期刊：
影响因子：
5.7
通讯作者：
Imaizumi, Nobutoshi
中科院分区：
文献类型：
--
作者：
Yin, Guang;Kono, Suminori;Imaizumi, Nobutoshi
乙醇脱氢酶和乙醛脱氢酶是酒精代谢的关键酶，因此可能在结直肠癌的发生发展中起重要作用。为探讨ADH2、ADH3和ALDH2基因多态性对日本福冈地区结直肠癌发病的影响，本研究从福冈地区随机抽取685例结直肠腺癌病例和778例社区对照进行病例对照研究。酒精使用是通过面谈来确定的。对性别、年龄段、地区和饮酒情况进行了统计调整。携带ADH2基因47Arg等位基因(代谢缓慢者)的个体与携带ADH2*47His/His基因的个体相比，风险显著增加，调整后的OR值为1.32(95%CI=1.07~1.63)。这种联系不受饮酒水平的影响。在总体分析或饮酒分层分析中，ADH3基因多态与结直肠癌风险没有可测量的相关性。ALDH2*487Glu/Lys杂合子与ALDH2*487Glu/Glu杂合子相比，与ALDH2*487Glu/Glu杂合子相比，并不增加患结直肠癌的风险(调整后OR为0.89，95%CI=0.71~1.13)。更令人意外的是，ALDH2*487Lys/Lys纯合子基因与结直肠癌风险显著降低相关(调整后OR为0.55，95%CI=0.33-0.93)。ALDH2基因多态决定的乙醛代谢不太可能增加结直肠癌的风险，而ADH2基因多态的作用值得进一步研究。
Alcohol dehydrogenase and aldehyde dehydrogenase are key enzymes in alcohol metabolism and therefore may be of importance to colorectal cancer development. The present case-control study was conducted to determine the influence of ADH2, ADH3 and ALDH2 polymorphisms in Fukuoka, Japan, with 685 incident cases of histologically confirmed colorectal adenocarcinomas and 778 community controls selected randomly from the study area. Alcohol use was ascertained by in-person interview. Statistical adjustment was made for sex, age class, area, and alcohol use. Individuals with the allele 47Arg of the ADH2 polymorphism (slow metabolizers) had a statistically significant increase in risk, with an adjusted OR of 1.32 (95% CI = 1.07-1.63), compared with those having the ADH2*47His/His genotype. This association was not affected by the level of alcohol consumption. The ADH3 polymorphism showed no measurable association with the risk of colorectal cancer on either overall analysis or stratified analysis with alcohol use. The heterozygous ALDH2*487Glu/Lys genotype was not associated with an increase in the risk of colorectal cancer (adjusted OR 0.89, 95% CI = 0.71-1.13) compared with the ALDH2*487Glu/Glu genotype. Rather unexpectedly, the homozygous ALDH2*487Lys/Lys genotype was related to a statistically significantly decreased risk of colorectal cancer (adjusted OR 0.55, 95% CI = 0.33-0.93). It is unlikely that acetaldehyde metabolism determined by ALDH2 polymorphism contributes to the risk of colorectal cancer, whereas the role of ADH2 polymorphism deserves further investigation.