title: Tagging SNPs in the ERCC4 gene are associated with gastric cancer risk.
abstract: 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.
authors.affiliation: Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Chu
authors.forename: Qinghong
authors.initials: Q
authors.lastname: Zhao
authors.forename: Shizhi
authors.initials: S
authors.lastname: Wang
authors.forename: Meilin
authors.initials: M
authors.lastname: Wang
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
authors.forename: Dewei
authors.initials: D
authors.lastname: Luo
authors.forename: Yongfei
authors.initials: Y
authors.lastname: Tan
authors.forename: Weida
authors.initials: W
authors.lastname: Gong
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Dongmei
authors.initials: D
authors.lastname: Wu
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012907:Smoking; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; C095888:xeroderma pigmentosum group F protein