RT Journal Article
SR Electronic
T1 Genetic Variants Associated with the Risk of Chronic Obstructive Pulmonary Disease with and without Lung Cancer
JF Cancer Prevention Research
JO Cancer Prev Res (Phila)
FD American Association for Cancer Research
SP 365
OP 373
DO 10.1158/1940-6207.CAPR-11-0243
VO 5
IS 3
A1 de Andrade, Mariza
A1 Li, Yan
A1 Marks, Randolph S.
A1 Deschamps, Claude
A1 Scanlon, Paul D.
A1 Olswold, Curtis L.
A1 Jiang, Ruoxiang
A1 Swensen, Stephen J.
A1 Sun, Zhifu
A1 Cunningham, Julie M.
A1 Wampfler, Jason A.
A1 Limper, Andrew H.
A1 Midthun, David E.
A1 Yang, Ping
YR 2012
UL http://cancerpreventionresearch.aacrjournals.org/content/5/3/365.abstract
AB Chronic obstructive pulmonary disease (COPD) is a strong risk factor for lung cancer. Published studies about variations of genes encoding glutathione metabolism, DNA repair, and inflammatory response pathways in susceptibility to COPD were inconclusive. We evaluated 470 single-nucleotide polymorphisms (SNP) from 56 genes of these three pathways in 620 cases and 893 controls to identify susceptibility markers for COPD risk, using existing resources. We assessed SNP- and gene-level effects adjusting for sex, age, and smoking status. Differential genetic effects on disease risk with and without lung cancer were also assessed; cumulative risk models were established. Twenty-one SNPs were found to be significantly associated with risk of COPD (P < 0.01); gene-based analyses confirmed two genes (GCLC and GSS) and identified three additional genes (GSTO2, ERCC1, and RRM1). Carrying 12 high-risk alleles may increase risk by 2.7-fold; eight SNPs altered COPD risk without lung cancer by 3.1-fold and 4 SNPs altered the risk with lung cancer by 2.3-fold. Our findings indicate that multiple genetic variations in the three selected pathways contribute to COPD risk through GCLC, GSS, GSTO2, ERCC1, and RRM1 genes. Functional studies are needed to elucidate the mechanisms of these genes in the development of COPD, lung cancer, or both. Cancer Prev Res; 5(3); 365–73. ©2011 AACR.