Genetic Polymorphisms of CYP2E1 and Risk of Colorectal Cancer: The Fukuoka Colorectal Cancer Study
Genetic Polymorphisms of CYP2E1 and Risk of Colorectal Cancer: The Fukuoka Colorectal Cancer Study
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DOI：
10.1158/1055-9965.epi-08-0698
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发表时间：
2009-01-01
影响因子：
3.8
通讯作者：
Imaizumi, Nobutoshi
中科院分区：
文献类型：
--
作者：
Morita, Makiko;Le Marchand, Loic;Imaizumi, Nobutoshi
细胞色素P450 2E1 （CYP2E1）参与多种潜在致癌物的代谢激活，CYP2E1基因的功能多态性与结直肠癌的关系已被研究。我们研究了CYP2E1 RsaI和96-bp插入多态性与结直肠癌风险的关系，以及这些多态性与一些生活方式危险因素之间的相互作用。研究对象为685例结直肠癌病例和778例社区对照。对饮酒、体重指数、体力活动和其他因素进行统计调整。RsaI c2等位基因与直肠癌风险降低相关[至少一个c2等位基因的校正优势比为0.71；95%可信区间（95% CI）， 0.53-0.95]，并且在具有一个或两个96-bp插入等位基因的个体中观察到直肠癌的风险增加（校正优势比，1.40;95% CI, 1.06-1.85）。具有两个96 bp插入等位基因的个体结肠癌风险增加2.28倍（95% CI, 1.29-4.01）。两个多态性几乎处于完全连锁不平衡状态（D′= 0.94）。仅在没有RsaI c2等位基因的个体（P-trend = 0.03）或没有96-bp插入等位基因的个体（P-trend = 0.009）中观察到酒精摄入与结直肠癌之间的正相关。只有在有一个或两个96-bp插入等位基因的个体中，与红肉摄入量相关的结肠癌风险才会增加（p相互作用= 0.03）。目前的研究表明，与酒精或红肉摄入量有关的CYP2E1活性和诱导性的变化有助于结直肠癌的发展。（癌症流行病学杂志，2009;18(1):235-41）
Cytochrome P450 2E1 (CYP2E1) is involved in the metabolic activation of a wide variety of potential carcinogens, and functional polymorphisms in the CYP2E1 gene have been investigated in relation to colorectal cancer. We examined the relation of the CYP2E1 RsaI and 96-bp insertion polymorphisms to colorectal cancer risk and the interaction between these polymorphisms and some lifestyle risk factors. Subjects were 685 incident cases of colorectal cancer and 778 community controls. Statistical adjustment was made for alcohol use, body mass index, physical activity, and other factors. The RsaI c2 allele was associated with a decreased risk of rectal cancer [adjusted odds ratio for at least one c2 allele, 0.71; 95% confidence interval (95% CI), 0.53-0.95], and an increased risk of rectal cancer was observed among individuals having one or two 96-bp insertion alleles (adjusted odds ratio, 1.40; 95% CI, 1.06-1.85). Individuals with two 96-bp insertion alleles showed a 2.28-fold increase in colon cancer risk (95% CI, 1.29-4.01). The two polymorphisms were in almost complete linkage disequilibrium (D' = 0.94). A positive association between alcohol intake and colorectal cancer was observed only in individuals without RsaI c2 allele (P-trend = 0.03) or in those without 96-bp insertion allele (P-trend = 0.009). Colon cancer risk was increased in relation to red meat intake only in individuals having one or two 96-bp insertion alleles (P-interaction = 0.03). The present study suggests that variation in activity and inducibility of CYP2E1, in relation to alcohol or red meat intake, contributes to the development of colorectal cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(1):235-41)