XRCC1单核苷酸多态性与结直肠癌风险的关系

背景与目的:X线交叉互补基因1(X-ray repair cross complementing group 1,XRCC1)编码蛋白在DNA单链断裂修复和DNA碱基修复过程中起重要作用.该基因外显子多态性的存在可影响编码蛋白的功能活性,最终使机体对癌症的易感性发生变化.本研究旨在探讨该基因外显子最常见的3处单核苷酸多态(single nucleotide polymorphism,SNP)--C26304T、G27466A和G28152A与结直肠癌风险的关系.方法:以聚合酶链反应(polymerase chain reaction,PCR)和限制性片段长度多态性(restrictive fragment length polymorphism,RFLP)分析方法,检测207例结直肠癌病例和621例成组匹配的正常对照XRCC1 C26304T、G27466A和G28152A基因型,并比较不同基因型与结直肠癌风险的关系.采用EH Linkage Software 1.2统计分析软件对研究对象的单体型分布进行预测.结果:年龄、性别、身体质量指数(body mass index,BMI)等个体特征,以及吸烟、饮酒等常见环境暴露因素的分布和/或构成比在结直肠癌病例组和对照组间差异均无显著性(P＞0.05).对XRCC1各多态基因型检测分型发现,结直肠癌病例组携带26304T、27466A和28152A变异等位基因的频率分别为29.95%、11.22%和28.22%,对照组分别为32.87%、12.34%和27.27%,各多态等位基因在两组间分布均没有显著性差异(P＞0.05).各多态基因型分布经x2拟合优度检验均符合Hardy-Weinberg平衡定律,且在两组间都没有显著性差异(P＞0.05).没有观察到各多态基因型与结直肠癌发病风险存在显著相关关系(P＞0.05).单体型分析发现,各变异等位基因在病例组和对照组内均存在遗传连锁不平衡现象,CGG、CGA、CAG和TGG是最常见的4类单体型,其在两组的分布频率总和分别为95.54%和96.64%,然而在两组间同样不存在显著性差异(P＞0.05).结论:我国浙江省嘉善县人群中,XRCC1 C26304T、G27466A和G28152A基因多态性与结直肠癌发病风险不存在相关性,然而各变异等位基因存在遗传连锁不平衡现象,CGG、CGA、CAG和TGG是最常见的4类单体型.

Correlations of single nucleotide polymorphisms of DNA repair gene XRCC1 to risk of colorectal cancer

BACKGROUND & OBJECTIVE: X-ray repair cross complementing group 1 (XRCC1) encodes a protein required for DNA base excision repair and single strand break recombination repair. The polymorphisms of XRCC1 affect the function of the protein, therefore, affect the susceptibility of human to cancers. This population-based case-control study was to examine the correlations of the 3 most common single nucleotide polymorphisms (SNPs) of XRCC1 gene, C26304T, G27466A and G28152A, to risk of colorectal cancer. METHODS:XRCC1 genotypes in 207 colorectal cancer patients and 621 matched healthy controls were analyzed by polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP). The adjusted odds ratio (OR) and 95% confidence interval (CI) were calculated using unconditional logistic regression model to evaluate the correlations of the 3 genotypes to risk of colorectal cancer. The haplotype distribution was estimated by EH linkage software 1.2. RESULTS: There was no significant differences in selected characteristics, such as age, sex, body mass index, cigarette-smoking and alcohol-drinking status, between the patients and the controls. The frequencies of mutant 26304T, 27466A, and 28152A alleles were 29.95%, 11.22%, and 28.22%, respectively, in the patients, and 32.87%, 12.34%, and 27.27%, respectively, in the controls; there was also no significant difference between the 2 groups. All the polymorphic genotypes met the Hardy-Weinberg equilibrium. No significant correlation of XRCC1 C26304T, G27466A, and G28152A polymorphisms to risk of colorectal cancer was found. Estimated by EH linkage software 1.2, genetic linkage disequilibrium existed both in the patients and the controls, and CGG, CGA, CAG, and TGG were the 4 most common haplotypes. However, there was no significant difference in haplotype distribution between the 2 groups (95.54% vs. 96.64%, P>0.05). CONCLUSIONS: In Han people in southern China, XRCC1 C26304T, G27466A, and G28152A polymorphisms have no correlations to risk of colorectal cancer. However, the genetic linkage disequilibrium exists in these 3 polymorphic sites, and CGG, CGA, CAG, and TGG are the 4 most common haplotypes.