DNA修复基因ADPRT和XRCC1遗传变异与胃癌发病风险  

Correlation of Genetic Polymorphisms in DNA Repair Genes ADPRT and XRCC1 to Risk of Gastric Cancer

作　　者：张志 缪小平[2] 谭文[2] 郭永丽[2] 张雪梅[2] 林东昕[2] 

机构地区：[1]河北省唐山市工人医院肿瘤放化疗科,河北唐山063000 [2]中国医学科学院中国协和医科大学肿瘤研究所病因及癌变研究室,北京100021

出　　处：《癌症》2006年第1期7-10,共4页Chinese Journal of Cancer

基　　金：北京市科委重大项目(No.H0209-20030130);国家杰出青年科学基金(No.39825122)~~

摘　　要：背景与目的:DNA修复缺陷是肿瘤的遗传易感因素。二磷酸腺苷核糖转移酶(adenosinediphosphateribosyltransferase,ADPRT)和X线修复交叉互补蛋白1(X-rayrepaircross-complementing1,XRCC1)是碱基切除修复的重要成分。这两个修复蛋白基因均存在功能性遗传。本研究探讨ADPRT762Val→Ala和XRCC1399Arg→Gln变异单独或联合与胃癌发生风险的关系。方法:以聚合酶链反应-限制性片段长度多态分析方法,检测236例胃癌患者和708例无肿瘤正常对照的基因型。以logistic多因素回归模型计算各基因型的胃癌风险以及基因-基因交互作用对胃癌风险的影响。结果:ADPRTAla/Ala基因型患胃癌的风险比ADPRTVal/Val基因型高2倍(OR=2.07;95%CI=1.33～3.21;P=0.001)。XRCC1399Arg→Gln变异单独与胃癌风险无关,但与ADPRT基因型存在基因-基因交互作用,携带ADPRTAla/Ala和XRCC1Gln/Gln基因型者患胃癌的风险比携带ADPRTVal/Val和XRCC1Arg/Arg者高5.32倍(95%CI=1.12～28.57;P<0.001)。结论:ADPRT762Val→Ala变异是胃癌的遗传易感因素,而XRCC1399Arg→Gln变异有促进ADPRT762Val→Ala的作用。BACKGROUND ＆ OBJECTIVE： Adenosine diphosphate ribosyl transferase （ADPRT） and X-ray repair cross-complementing 1 （XRCC1） are 2 major DNA base excision repair （BER） proteins and act interactively in stimulating and executing BER processes. Polymorphisms of ADPRT 762Val→ Ala and XRCC1 399Arg→GIn have been verified to associate with altered protein function and BER activity. This study was to examine the contribution of these 2 polymorphisms, alone or in combination, to the risk of developing gastric cancer. METHODS： A total of 236 patients with gastric cancer and 708 cancer-free controls were genotyped for the 2 polymorphisms by polymerase chain reaction-restrictive fragment length polymorphism （PCRRFLP） method. Odds ratio （OR） and 95% confidence interval （CI） were calculated using unconditional logistic regression model to evaluate the impact of these 2 polymorphisms on the risk of developing gastric cancer. RESULTS： The subjects having the ADPRT Ala/Ala genotype had an OR of 2.07 （95% CI=1.33-3.21 ; P=0.001 ） compared with those having the Val/Val genotype. Gene-gene interaction of ADPRT and XRCC1 polymorphisms increased the risk of gastric cancer in a super-multiplicative manner, with an OR of 5.32 （95% CI=1.12-28.57） for the presence of both ADPRT 762Ala/ Ala and XRCC1 399Gin/Gin genotypes, although the XRCC1 polymorphism itself was not associated with the risk of gastric cancer. CONCLUSION： The ADPRT 762Val→Ala polymorphism plays an important role in the development of gastric cancer, and the XRCC1 399Arg→GIn polymorphism may serve as a risk modifier.

关 键 词：胃肿瘤/遗传学 ADPRT XRCC1 遗传易感性 多态 

分 类 号：R735.2[医药卫生—肿瘤]