title: Potentially functional polymorphisms in DNA repair genes and non-small-cell lung cancer survival: a pathway-based analysis.
abstract: To assess systematically whether potentially functional polymorphisms in DNA repair genes influence the clinical behavior of non-small-cell lung cancer (NSCLC), we examined the impact of a comprehensive panel of 218 signal nucleotide polymorphisms (SNP) in 50 candidate DNA repair genes on overall survival of NSCLC in a case-cohort of 568 lung cancer patients. SNPs associated with lung cancer prognosis primarily mapped to 14 genes in different repair pathways, and 6 SNPs were remained in the final model after multivariate stepwise Cox regression analysis: ATM rs189037; MRE11A rs11020802; ERCC2 rs1799793; MBD4 rs140693; XRCC1 rs25487, and PMS1 rs5742933. In the combined analysis of these 6 SNPs, an increasing number of unfavorable loci was associated with a poorer prognosis (P for trend: <0.0001) and patients having 2-4 unfavorable loci had a 1.99-fold elevated risk of death 95% confidence interval (CI) = 1.58-2.50, compared with those carrying 0-1 unfavorable loci, and this elevated risk was more evident among stages I-II patients (hazard ratio = 3.04, 95% CI = 1.86-4.98, P for heterogeneity: 0.07). Furthermore, a significant effect of SNPs in nucleotide excision repair pathway on lung cancer survival was observed among 185 stages III-IV patients treated with platinum-based chemotherapy without surgical operation: XPC rs2228000 (Ala499Val; P = 0.002) and ERCC1 rs11615 (Asn118Asn; P = 0.012). Our data indicate that potentially functional polymorphisms in DNA repair genes may serve as candidate prognostic markers of clinical outcome of NSCLC.
authors: Department of Epidemiology and Biostatistics, MOE Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors: Jing
authors: J
authors: Dong
authors: Zhibin
authors: Z
authors: Hu
authors: Yongqian
authors: Y
authors: Shu
authors: Shiyang
authors: S
authors: Pan
authors: Wenping
authors: W
authors: Chen
authors: Yi
authors: Y
authors: Wang
authors: Lingmin
authors: L
authors: Hu
authors: Yue
authors: Y
authors: Jiang
authors: Juncheng
authors: J
authors: Dai
authors: Hongxia
authors: H
authors: Ma
authors: Guangfu
authors: G
authors: Jin
authors: Hongbing
authors: H
authors: Shen
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D016019:Survival Analysis