Tagging SNPs in the ERCC4 gene are associated with gastric cancer risk

详细信息    查看全文

• 作者：Haiyan Chu^a ; ^b ; ¹ ; Qinghong Zhao^c ; ¹ ; Shizhi Wang^a ; ^b ; Meilin Wang^a ; ^b ; Ming Xu^a ; ^b ; Yan Gao^a ; ^b ; Dewei Luo^a ; ^b ; Yongfei Tan^d ; Weida Gong^e ; Zhengdong Zhang^a ; ^b ; ^{drzdzhang@gmail.com} ; Dongmei Wu^a ; ^b ; ^{dmwu623@gmail.com}
• 关键词：NER ; nucleotide excision repair ; SNPs ; single nucleotide polymorphisms ; tSNPs ; tagging SNPs ; LR ; logistic regression ; OR ; odds ratio ; 95 % CI ; 95 % confidence interval ; MDR ; multifactor dimensionality reduction ; CVC ; cross-validation consistency ; ERCC4 ; exc
• 刊名：Gene
• 出版年：2013
• 出版时间：25 May, 2013
• 年：2013
• 卷：521
• 期：1
• 页码：50-54
• 全文大小：232 K

文摘

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.