A gene-gene interaction between ALDH2 Glu487Lys and ADH2 His47Arg polymorphisms regarding the risk of colorectal cancer in Japan
A gene-gene interaction between ALDH2 Glu487Lys and ADH2 His47Arg polymorphisms regarding the risk of colorectal cancer in Japan
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DOI：
10.1093/carcin/bgi282
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发表时间：
2006-05-01
期刊：
影响因子：
4.7
通讯作者：
Tajima, K
中科院分区：
文献类型：
--
作者：
Matsuo, K;Wakai, K;Tajima, K
饮酒被认为是结直肠癌(CRC)的潜在危险因素。乙醛脱氢酶(ALDH2)Glu487Lys和乙醇脱氢酶2(ADH2)His47Arg基因多态性对酒精代谢有强烈影响，在日本人群中很常见，但它们在结直肠癌发生中的意义仍有待详细阐明。因此，我们在爱知癌症中心对257例结直肠癌病例和771例非癌症对照进行了配对的病例对照研究，包括分析基因多态、饮酒和叶酸摄入之间的相互作用。His/Arg和Arg/Arg两种等位基因的优势比(OR)分别为1.35(95%可信区间：1.00~1.84)和1.93(1.06~3.53)。相反，未观察到ALDH2基因与ALDH2的明显关联。ALDH2 Glu/Glu与ADH2 Arg+、ALDH2 Lys+与ADH2 His/His、ALDH2 Lys+与ADH2 Arg+的OR值分别为0.10(0.04~0.21)、0.10(0.06~0.19)和1.36(0.94~1.97)。两个多态之间的基因-基因交互作用对结直肠癌的风险有显著的统计学意义(P<；0.001)。ALDH2 Lys+和ADH2 Arg+在低叶酸消费者(OR=2.32，1.19~4.55)中的影响比高叶酸消费者(OR 1.38，0.80~2.38)更明显。总之，虽然我们没有发现与ALDH2多态本身有任何显著的关联，但观察到ALDH2和ADH2多态之间存在显著的交互作用。在未来的研究中有必要进行重复试验。
Alcohol consumption is recognized as a potential risk factor for colorectal cancer (CRC). Genetic polymorphisms, aldehyde dehydrogenase (ALDH2) Glu487Lys and alcohol dehydrogenase 2 (ADH2) His47Arg, which have a strong impact on alcohol metabolism, are common in Japanese population but their significance for CRC carcinogenesis remains to be clarified in detail. We, therefore, conducted a matched case-control study with 257 incident CRC cases and 771 non-cancer controls at Aichi Cancer Center, including analysis of interactions between polymorphisms, drinking and folate consumption. The ADH2 Arg allele was found to be associated with increased risk, the odds ratios (ORs) being 1.35 (95% confidence interval: 1.00-1.84) and 1.93 (1.06-3.53) for the His/Arg and Arg/Arg genotypes, respectively. In contrast, no apparent links were observed with the ALDH2 genotypes. Individuals having ALDH2 Glu/Glu with ADH2 Arg+, ALDH2 Lys+ with ADH2 His/His and ALDH2 Lys+ with ADH2 Arg+ showed ORs of 0.10(0.04-0.21), 0.10 (0.06-0.19) and 1.36 (0.94-1.97), respectively, compared with ALDH2 Glu/Glu with ADH2 His/His. Statistical gene-gene interaction was significant between the two polymorphisms for the risk of CRC (P < 0.001). The impact of ALDH2 Lys+ with ADH2 Arg+ was more evident in low folate consumer (OR = 2.32, 1.19-4.55) than high folate consumer (OR 1.38, 0.80-2.38). In conclusion, while we failed to find any significant association with the ALDH2 polymorphism itself, significant interaction between ALDH2 and ADH2 polymorphism was observed. Replication in the future study is warranted.