Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
Gene. 2013 May 25;521(1):50-4. doi: 10.1016/j.gene.2013.03.046. Epub 2013 Mar 26.
ERCC4 plays an essential role in the nucleotide excision repair (NER) pathway, which is involved in the removal of a wide variety of DNA lesions. To determine whether the ERCC4 tagging SNPs (tSNPs) are associated with risk of gastric cancer, we conducted a hospital-based case-control study of 350 cases and 468 cancer-free controls. In the logistic regression (LR) analysis, we found a significantly decreased risk of gastric cancer associated with the rs744154 GC/CC genotypes [adjusted odds ratio (OR)=0.56, 95% confidence interval (CI)=0.42-0.75, false discovery rate (FDR) P=0.003] compared with the wild-type GG genotype. Haplotype-based association study revealed that the CGC haplotype that containing the rs744154 C allele can decrease the risk of gastric cancer compared with the most common haplotype GGT (adjusted OR=0.61, 95% CI=0.46-0.81). Using the multifactor dimensionality reduction (MDR) analysis, we identified that the SNP rs744154 and smoking status were the best two predictive factors for gastric cancer with a testing accuracy of 55.76% and a perfect cross-validation consistency (CVC) of 10 (P=0.001). Furthermore, the smokers with the rs744154 GC/CC genotypes showed a decreased risk of gastric cancer (adjusted OR=0.55, 95% CI=0.35-0.85) compared with the smokers with the GG genotype using multivariate LR analysis. The above findings consistently suggested that genetic variants in the ERCC4 gene may play a protective role in the etiology of gastric cancer, even in the smokers.
ERCC4 在核苷酸切除修复（NER）途径中发挥着重要作用，该途径参与了多种 DNA 损伤的清除。为了确定 ERCC4 标签 SNP（tSNP）是否与胃癌风险相关，我们进行了一项基于医院的病例对照研究，共纳入 350 例病例和 468 例无癌对照。在逻辑回归（LR）分析中，我们发现与野生型 GG 基因型相比，rs744154GC/CC 基因型与胃癌风险显著降低相关[调整后的优势比（OR）=0.56，95%置信区间（CI）=0.42-0.75，假发现率（FDR）P=0.003]。基于单倍型的关联研究表明，与最常见的单倍型 GGT 相比，包含 rs744154C 等位基因的 CGC 单倍型可降低胃癌风险[调整后的 OR=0.61，95%CI=0.46-0.81]。使用多因子降维（MDR）分析，我们发现 rs744154 与吸烟状态是预测胃癌的最佳两个因素，其检测准确率为 55.76%，完美交叉验证一致性（CVC）为 10（P=0.001）。此外，在多变量 LR 分析中，与 GG 基因型的吸烟者相比，rs744154GC/CC 基因型的吸烟者胃癌风险降低（调整后的 OR=0.55，95%CI=0.35-0.85）。以上发现一致表明 ERCC4 基因中的遗传变异可能在胃癌的病因学中发挥保护作用，即使在吸烟者中也是如此。
