RAD18基因rs373572位点多态性与结直肠癌的相关性研究

Correlation of RAD18 Gene rs373572 Polymorphism with Colorectal Cancer

背景：RAD18是一种单链DNA结合蛋白,在维持受损DNA的完整性和细胞基因组稳定等方面起有重要作用。目的：研究RAD18基因单核苷酸多态性（SNPs）位点Arg302Gln（rs373572）与结直肠癌易感性及其临床病理特征的关系。方法：提取109例结直肠癌患者和241名健康对照者的外周血基因组DNA,采用PCR测序法对RAD18基因rs373572位点进行基因分型。结果：结直肠癌组与对照组间RAD18基因rs373572位点GG、GA、AA基因型分布差异有统计学意义（P〈0.05）,结直肠癌组AA基因型频率显著高于对照组（16.5%对8.7%,P〈0.05;校正后OR=2.428,95%CI：1.170-5.035）,有远处转移的结直肠癌患者GA基因型频率显著高于无远处转移者（75.0%对41.9%,P〈0.05;校正后OR=7.764,95%CI：0.927-65.206）。rs373572位点多态性与结直肠癌分化程度、肿瘤部位、Duke分期、淋巴结转移均无相关性（P〉0.05）。结论：RAD18基因rs373572位点AA基因型可能是结直肠癌的遗传易感因素,且该位点多态性与结直肠癌的远处转移有关。

Background： RAD18 is a single stranded DNA binding protein,which plays an important role in maintaining the integrity of damaged DNA and the genomic stability of cells. Aims： To study the correlation of Arg302Gln（ rs373572）,a single nucleotide polymorphism（ SNP） in RAD18 gene,with the susceptibility and clinicopathological features of colorectal cancer（ CRC）. Methods： Peripheral blood genomic DNA of 109 CRC patients and 241 healthy subjects were extracted and went through gene sequencing after PCR amplification for RAD18 rs373572 genotyping. Results： Statistically significant differences were found in distribution of RAD18 rs373572 GG,GA and AA genotypes between CRC and control groups（ P〈0. 05）; the frequency of AA genotype in CRC group was significantly higher than that in control group（ 16. 5% vs. 8. 7%,P〈0. 05; adjusted OR = 2. 428,95% CI： 1. 170-5. 035）. In CRC group,GA genotype was more frequent in patients with distant metastasis than those without（ 75. 0% vs. 41. 9%,P〈0. 05; adjusted OR = 7. 764,95%CI： 0. 927-65. 206）. No correlation was found between rs373572 polymorphism and differentiation,location,Duke＇s stage and lymph node metastasis of CRC（ P〉0. 05）. Conclusions： RAD18 rs373572 AA genotype might be a genetic susceptible factor for CRC,and rs373572 polymorphism is correlated with distant metastasis of CRC.