乙醇代谢酶类基因多态性及环境暴露在结直肠癌发生中交互作用的单纯病例研究  

Role of alcohol-metabolizing enzymes gene polymorphisms and environmental exposure on colorectal cancer： a case-only study

作　　者：赵浩[1,2] 李婷婷[1] 尹洁云[1] 秦芹[1] 师芸[1] 田丽红[1] 聂绍发[1] 汪鑫[3] 刘莉[1] 

机构地区：[1]华中科技大学同济医学院公共卫生学院流行病与卫生统计学系,武汉430030 [2]南昌大学公共卫生学院 [3]九江学院医学院

出　　处：《中华流行病学杂志》2013年第10期1013-1017,共5页Chinese Journal of Epidemiology

基　　金：国家自然科学基金（30972534）

摘　　要：目的研究环境因素与乙醇脱氢酶1B（ADH1B）rs1229984、乙醛脱氢酶2（ALDH2）rs671、细胞色素P4502E1（CYP2E1）rs1329149交互及基因一基因之间交互在结直肠癌发生中的作用，分析该3个基因位点对结直肠癌发展的影响。方法采用单纯病例研究调查472例结直肠癌患者环境暴露情况和病理分期，用SequenomMassARRAY系统检测ADH1B（rs1229984）、ALDH2（rs671）、CYP2E1（rs1329149）的基因型，应用非条件1ogistic回归分析ADH1B、ALDH2、CYP2E1基因多态性与环境因素及基因一基因之间的交互作用，采用）c。检验及非条件1ogistic回归评估rs1229984、rs671、rs1329149与结直肠癌转移风险的关系。结果体重指数（BMI）与ADH1Brs1229984在结直肠癌发生中存在相乘交互作用（OR=1．720，95％CI：1．038～2．848，D‰=1．785，95％CI：1．061—3．002）；曾经或现在吸烟与ADH1B（rs1229984）的基因多态性在结直肠癌发生中存在交互作用，经调整性别、年龄和饮酒后，该交互作用消失（OR=O．597，95％C／：0．387．0．921，ORadj=0．922，95％CI：0．509～1．669）；rs1229984、rs671、rs1329149与结直肠癌的转移风险无关。结论超重（BM17〉25kg／m2）R携带ADH1Brs1229984G易感等位基因可能增加结直肠癌发生的危险陛，rs1229984、rs671、rs1329149与结直肠癌的转移无关。Objective This study was designed to explore the interactions of alcohol dehydrogenase 1B （ADH1B） rs1229984, aldehyde dehydrogenase 2 （ALDH2） （rs671） and cytochrome P4502E1 （CYP2E1） rs1329149 with environmental factors and the interactions between genetic factors in the susceptibility of colorectal cancer （CRC）. Roles of genetic factors in the development of colorectal cancer were also studied. Methods With a case-only study design, 472 colorectal cancer cases were enrolled between 2007 and 2009 in this study. Data on demographic characteristics, histories of environmental exposure and clinico-pathological parameters were obtained from all the participants through written questionnaires. Genotypes were determined by Sequenom MassARRAY system. Unconditional logistic regression analysis was employed to explore the gene-environment interactions and gene-gene interactions. Z2 test and unconditional logistic regression were used to evaluate the roles of polymorphisms on the risk of metastasis to CRC. Results Overweighted individuals that carrying at least one of the ADH1B rs1229984 G alleles presented significant increase on the risk to colorectal cancer （OR= 1.720, 95%CI： 1.038-2.848, ORadj= 1.785, 95%C1： 1.061-3.002）. Modest interaction was seen between smoking and ADH1B （rs1229984） only before the adjustment of data, by sex, age and drinking status （OR=0.597, 95% CI： 0.387-0.921, ORadj=0.922,95% CI： 0.509-1.669）. Correlations between polymorphisms and the Dukes stage were not found. Conclusion Overweight presented significant interaction with G allele of ADH1B rs1229984 in the susceptibility of CRC. None of the rs1229984, rs671 and rs1329149 exhibited significant influence on the development of CRC.

关 键 词：结直肠癌 基因一环境交互作用 基因一基因交互作用 单纯病例研究 

分 类 号：R735.3[医药卫生—肿瘤]