ALDH2和CYP2E1基因多态性及饮酒习惯与肝细胞癌易感性的关系  

Association between aldehyde dehydrogenase-2/cytochrome P450 2E1 genetic polymorphism and habit of alcohol drinking and the susceptibility of hepatocellular carcinoma

作　　者：叶新平[1] 彭涛[1] 刘唐威[1] 苏智雄[1] 肖开银[1] 尚丽明[1] 苏铭[1] 黎乐群[1] 

机构地区：[1]广西医科大学第一附属医院肝胆外科,南宁530021

出　　处：《卫生研究》2010年第1期42-45,共4页Journal of Hygiene Research

基　　金：国家自然科学基金资助项目(No.30460143);广西科技开发计划项目(桂科攻No.0632007-1E)

摘　　要：目的研究乙醛脱氢酶2(ALDH2)和细胞色素P4502E1(CYP2E1)基因多态性与饮酒因素交互作用在广西原发性肝细胞癌发生中的作用。方法对广西壮族自治区300例肝细胞癌和292例正常对照进行流行病学调查研究,并用PCR-RFLP方法检测ALDH2和CYP2E1基因型。结果病例和对照组中ALDH2和CYP2E1变异基因型携带者分别占50.3%、48.0%和32.3%、32.9%(P>0.05)。饮酒频度每周≥3次(高频饮酒)且携带变异基因ALDH2和CYP2E1者发生肝癌的危险度分别是饮酒频度每周<3次(低频饮酒)且携带野生基因型者的3.334倍(95%CI=1.746～6.406)和1.803倍(95%CI=0.974～3.336),同时携带两变异基因型者患肝癌风险为1.200倍(95%CI=0.730～1.972),且饮酒增加两变异基因型携带者的肝癌发病风险(OR=1.816,95%CI=0.985～3.348)。结论单一ALDH2或CYP2E1基因型与肝细胞癌易感性无关;但高频饮酒且携带变异基因ALDH2或CYP2E1者患肝癌风险增加,且两变异基因型单倍体增加肝癌发病风险。提示乙醇在增加肝癌发病风险的过程中存在基因-环境和基因-基因相互作用。Objective To study the relationship between aldehyde dehydrogenase-2（ALDH2） and cytochrome P450 2E1（CYP2E1） gene polymorphism and alcohol drinking habit with the susceptibility of hepatocellular carcinoma（HCC）.Methods 300 cases of HCC and 292 controls were genotyped for the ALDH2 and CYP2E1 polymorphisms by using polymerase chain reaction-restriction fragment length polymorphism（ PCR-RFLP） method.Results The frequencies of ALDH2 and CYP2E1 variant genotypes in cases and controls were 50.3%,48.0% and 32.3%,32.9%,respectively.There was no significant difference of ALDH2 and CYP2E1 genotypes distribution between cases and controls （P〉0.05）.The risk for liver cancer was 3.334 times higher in alcoholics （≥3 times drinking per week） with ALDH22 genotype than that that in cases carrying ALDH21 genotype while drinking less than 3 times per week （95%CI=1.746-6.406）,and the risk for liver cancer was 1.803 times higher in alcoholics （≥3 times drinking per week） with CYP2E1c2 genotype than that in cases carrying CYP2E1c1 genotype while drinking less than 3 times per week （95%CI=0.974-3.336）.Haplatype of the two genotypes increased liver cancer risk to 1.200 folds （95%CI=0.730-1.972）,and interaction between drinking and genotypes increases risk of liver cancer to 1.816 folds （95%CI=0.985-3.348）.Conclusion ALDH2 or CYP2E1 genotypes alone render no significant risk for HCC,while frequent alcoholic consumption together with ALDH2 or CYP2E1 variant genotypes are assocoated with risk of hepatocarcinogenesis,suggesting a gene-environment interaction in increasing risk for HCC among Guangxi residents.

关 键 词：乙醛脱氢酶2 细胞色素P450 2E1 基因多态性 饮酒 肝肿瘤 

分 类 号：R735.7[医药卫生—肿瘤] Q593.1[医药卫生—临床医学]