Potentially functional polymorphisms in DNA repair genes and non-small-cell lung cancer survival: a pathway-based analysis.

Autor: Dong J; Department of Epidemiology and Biostatistics, MOE Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China., Hu Z, Shu Y, Pan S, Chen W, Wang Y, Hu L, Jiang Y, Dai J, Ma H, Jin G, Shen H
Jazyk: angličtina
Zdroj: Molecular carcinogenesis [Mol Carcinog] 2012 Jul; Vol. 51 (7), pp. 546-52. Date of Electronic Publication: 2011 Jul 07.
DOI: 10.1002/mc.20819
Abstrakt: 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.
(Copyright © 2011 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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