APE1 D148E、PARP1 V762A、XRCC1 R399Q的多态性与结直肠癌的易患性  

APE1 D148E,PARP1 V762A and XRCC1 R399Q polymorphisms and genetic susceptibility to colorectal cancer

作　　者：叶慈慈[1] 黄智铭[1] 周春燕[1] 

机构地区：[1]温州医学院附属第一医院消化内科,浙江省温州市325000

出　　处：《世界华人消化杂志》2010年第12期1275-1279,共5页World Chinese Journal of Digestology

摘　　要：目的:探讨APE1D148E、PARP1V762A及XRCC1R399Q的碱基切除修复基因单核苷酸多态位点对结直肠癌发病风险的修饰作用.方法:选取158例健康对照与123例原发性结直肠癌患者,提取外周血基因组DNA,用基质辅助激光解吸电离飞行时间(MALDI-TOF)质谱技术对SNP位点进行基因分型,在各混杂因素配比下,采用χ2检验比较病例组与对照组中各SNP的基因型分布差异以及多SNP的联合基因型分布差异,从而分析他们对结直肠癌风险的修饰程度OR值.结果:3个SNP在本研究中均符合Hardy-Weinberg平衡,其中只有XRCC1R399Q的GA/AA变异(V)型与结直肠癌发病有正相关性,OR值为1.633(95%CI:1.011-2.640,P=0.045);而APE1D148E、PARP1V762A的SNP变异单独对结直肠癌风险未见明显影响(P>0.05).联合基因型在两组比较显示,携带APE1(V)-PARP1(W)-XRCC1(V)者,结直肠癌发病风险是其他联合基因型携带者的2.604倍(95%CI:1.066-6.361,P=0.031);而其他联合基因型对结直肠癌风险的修饰作用则不明显.结论:XRCC1rs25487的GA/AA变异型是结直肠癌的危险因素;BER和SNP存在交互作用;携带联合基因型APE1(V)-PARP1(W)-XRCC1(V)者患结直肠癌的风险可能较高.AIM：To evaluate the possible effects of APE1 D148E,PARP1 V762A and XRCC1 R399Q single nucleotide polymorphisms （SNPs） on the risk of colorectal cancer （CRC）.METHODS：The APE1 D148E,PARP1 V762A and XRCC1 R399Q polymorphisms were analyzed in 123 patients with primary CRC and in 158 healthy controls using the matrix-assisted laser desorption/ionization-time of flight mass spectrometry （MALDI-TOF） method.After matching for potential confounding variables,the genotypes of each SNP site and combined genotypes of all included SNP sites were compared between case and control groups by the chi-square test.RESULTS：All three SNPs detected in the studymet the Hardy-Weinberg equilibrium.Only the frequency of XRCC1 R399Q GA/AA genotype was statistically higher in the case group than in the control group [odds ratio （OR）：1.633;95% confidence interval：1.011-2.640;P=0.045].APE1 D148E and PARP1 V762A polymorphisms did not yield any significant effects on the risk of CRC （P 〉0.05）.The combined genotype APE1 （V）-PARP1 （W）-XRCC1 （V） conferred a 2.604-fold increased risk of CRC compared with all other combined genotypes （95% confidence interval：1.066-6.361;P=0.031）.No other combined genotypes yielded any significant effects on the risk of CRC.CONCLUSION：XRCC1 R399Q GA/AA genotype may be a risk factor for CRC.There might be interactions among the SNPs of excision repair genes.APE1 （V）-PARP1 （W）-XRCC1 （V） carriers may have a higher risk of CRC.

关 键 词：DNA修复基因 结直肠癌 单核苷酸多态 碱基切除修复 

分 类 号：R735.3[医药卫生—肿瘤]