Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, 818 East Tianyuan Road, Nanjing 211166, China.
Mutagenesis. 2013 Jul;28(4):441-6. doi: 10.1093/mutage/get023. Epub 2013 May 16.
Endogenous and exogenous factors can induce DNA damage, leading to increased risk of cancer. Nucleotide excision repair (NER) is considered as the most versatile DNA repair pathway to deal with a variety of different DNA lesions. ERCC1 and ERCC2 are the two important proteins in NER pathway. In this study, we investigated the association of three functional single nucleotide polymorphisms (SNPs) (ERCC1 rs11615, ERCC2 rs13181 and ERCC2 rs1799793) with the clinical outcome of 940 gastric cancer patients in a Chinese population. Multiplex SNaPshot technology was used to genotype these three SNPs. Our results revealed that individuals with ERCC2 rs13181TG/GG genotypes had a decreased risk of death compared with those with TT genotype [log-rank P = 0.008; adjusted hazard ratio = 0.68, 95% confidence interval = 0.51-0.91] and this protective effect was more pronounced among the subgroups of patients with tumour size ≤ 5 cm (0.59, 0.39-0.89), non-cardia gastric tumour (0.69, 0.48-0.98), no lymph node metastasis (0.55, 0.32-0.96), no distant metastasis (0.70, 0.52-0.95) and chemotherapy (0.39, 0.21-0.72). We conclude that ERCC2 rs13181 polymorphism could play different roles in the overall survival of gastric cancer. Further larger studies should be conducted to validate our findings.
内源性和外源性因素可诱导 DNA 损伤,导致癌症风险增加。核苷酸切除修复 (NER) 被认为是处理各种不同 DNA 损伤的最通用的 DNA 修复途径。ERCC1 和 ERCC2 是 NER 途径中的两个重要蛋白。在这项研究中,我们调查了三个功能性单核苷酸多态性 (SNP) (ERCC1 rs11615、ERCC2 rs13181 和 ERCC2 rs1799793) 与中国人群 940 例胃癌患者临床结局的关联。采用多重 SNaPshot 技术对这三个 SNP 进行基因分型。我们的结果表明,与 TT 基因型相比,ERCC2 rs13181TG/GG 基因型的个体死亡风险降低[对数秩检验 P = 0.008;调整后的危险比 = 0.68,95%置信区间 = 0.51-0.91],这种保护作用在肿瘤大小≤5cm(0.59, 0.39-0.89)、非贲门胃肿瘤(0.69, 0.48-0.98)、无淋巴结转移(0.55, 0.32-0.96)、无远处转移(0.70, 0.52-0.95)和化疗(0.39, 0.21-0.72)的亚组中更为明显。我们的结论是,ERCC2 rs13181 多态性可能在胃癌的总生存中发挥不同的作用。需要进一步开展更大规模的研究来验证我们的发现。