结直肠腺癌遗传易感性与多药耐药基因多态性的关系

Association between multidrug resistance 1 gene polymorphisms and genetic susceptibility to sporadic colorectal adenocarcinoma

目的 探讨结直肠腺癌遗传易感性与多药耐药基因（MDR1）多态性的关系.方法 通过多重单碱基延伸反应（SnaPshot SNP分型技术）检测123例结直肠腺癌患者及386例健康对照者MDR1基因中C3435T、G2677T/A等位基因频率及基因型频率.分析正常人与结直肠腺癌患者C3435T、G2677T/A等位基因频率及基因型频率的差异.结果 在正常人及结肠腺癌患者中,C3435T、G2677T/A等位基因频率及基因型频率总体分布差异无统计学意义（P＞0.05）.结直肠腺癌组按性别、年龄、病变部位、分化程度、Dukes分期等临床病理特征分组后,C3435T基因型频率分布在结肠癌（CC 22.2％,CT 63.4％,TT 14.8％）和直肠癌（CC 50.7％,CT 31.9％,TT17.4％）患者中差异有统计学意义（P＜0.01）,等位基因3435T在直肠癌患者中的分布频率（33.3％）较结肠癌（46.3％）显著降低（P＜0.05）.与2677GG比较,2677GT基因型频率在中等分化腺癌（26.9％）中的分布较高分化（46.4％）和低分化腺癌（47.1％）显著降低（P＜0.05）,2677GT基因型频率在结肠癌患者（46.3％）中较直肠癌患者（24.6％）占明显优势（P＜0.05）.2677G等位基因在低分化腺癌（3.7％）的分布频率较中分化（28.5％）和高分化（11.0％）腺癌显著降低（P＜0.05）.结论 C3435T、G2677T/A位点基因多态性与结直肠腺癌无明显相关.

Objective To investigate the association between genetic polymorphism in exon 26 C3435T and exon 21 G2677T/A of the multidrug resistance 1 （MDR1） gene and the sporadic colorectal adenocarcinoma.Methods A total of 123 patients with colorectal adenocarcinoma and 86 healthy subjects as controls were included.Snapshot SNP typing was used to determine the allele and genotype frequencies of MDR1 C3435T,and G2677T/A.Results There was no significant difference in the distribution of MDR1 C3435T and G2677T/A alleles and genotypes frequencies between control group and case group.When stratified by clinicopathological features such as lesion distribution,differentiation degree and Duke＇ s stage in the patients with colorectal adenocarcinoma,the statistically significant differences were found in the frequency of C3435T genotype between patients with colon adenocarcinoma （CC 22.2%,CT 63.4%,and TT 14.8 %） and rectal adenocarcinoma （CC 50.7%,CT 31.9%,and TT 17.4%） （P 〈 0.01）.The frequency of 3435T allele was decreased significantly in patiens with rectal adenocarcinoma （33.3%） as compared with colon adenocarcinoma （46.3%,P 〈0.05）.And the frequency of 2677GT genotype was decreased significantly in patients with moderately-differentiated （26.9%） as compared with well-differentiated （46.4%） and poorly-differentiated （47.1%,P 〈 0.05）.Furthermore,the frequency of 2677GT genotype was increased significantly in patients with colon adenocarcinoma （46.3%） as compared with rectal adenocarcinoma （24.6%,P 〈 0.05）,and the frequency of 2677G allele was decreased significantly in patiens with poorly differentiated adenocarcinoma （3.7%） as compared with moderately-differentiated （28.5%） and well-differentiated adenocarcinoma （11.0%,P 〈 0.05）.Conclusion MDR1 C3435T and G2677T/A polymorphisms were found to be not associated with colorectal adenocarcinoma.