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OA04 - Epidemiology and Prevention of Lung Cancer (ID 370)
- Event: WCLC 2016
- Type: Oral Session
- Track: Epidemiology/Tobacco Control and Cessation/Prevention
- Presentations: 1
OA04.06 - Examining Pleiotropic Associations of Genetic Risk Variants for Chronic Obstructive Pulmonary Disease with Lung Cancer Risk (ID 5225)
11:00 - 12:30 | Author(s): N.H. Roubinian
Tobacco smoke is the primary cause of chronic obstructive pulmonary disease (COPD) and lung cancer, and among smokers, COPD is associated with increased lung cancer risk. However, fewer than 30% of smokers are diagnosed with either disease, suggesting that genetic factors also influence the pathogenesis of both diseases. Despite the plausibility for shared genetic predisposition, knowledge about pleiotropy between COPD and lung cancer is limited.
Using the Genetic Epidemiology Research on Adult Health and Aging cohort established at Kaiser Permanente Northern California (KPNC), an integrated healthcare system, we examined non-Hispanic white smokers aged ≥40 years diagnosed with lung cancer (n=489), including those with COPD (n=243) or without COPD (n=174), and neither disease (n=26,553) through January 31, 2014. Those with lung cancer were identified from KPNC Cancer Registry data. Those with COPD were identified from electronic health record data, requiring at least one hospitalization with a principal discharge diagnosis or two outpatient visits with a diagnosis of chronic bronchitis, emphysema, or COPD (ICD-9 codes: 491.*, 492.*, 496.*). We examined 16 single nucleotide polymorphisms (SNPs) in 10 risk loci identified previously for COPD or airflow obstruction by genome-wide association studies (1q41, 4q22.1, 4q31.21, 5q32, 6p21.32, 11q22, 14q32, 15q25.1, 16p11.2, 19q13) for their associations with lung cancer risk, overall and stratified by COPD. SNPs were examined individually and also jointly as an unweighted 16-SNP risk score. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression, adjusted for age, sex, pack-years of smoking, and principal components of genetic ancestry.
Only two SNPs at 15q25.1, a risk locus also known for lung cancer and nicotine dependence, were associated with overall lung cancer risk: rs8034191 (per-allele OR=1.22, 95% CI: 1.07-1.39, p=0.003) and rs12914385 (per-allele OR=1.23; 95% CI: 1.08-1.40, p=0.002). In stratified analyses, associations were marginally stronger for lung cancer without COPD (rs8034191: OR=1.36, 95% CI: 1.09-1.69; rs12914385: OR=1.24, 95% CI: 1.00-1.54) than lung cancer with COPD (rs8034191: OR=1.09, 95% CI: 0.90-1.31; rs12914385: OR=1.17, 95% CI: 0.97-1.40). The 16-SNP risk score was suggestively associated with overall lung cancer risk (highest vs. lowest quintile: OR=1.31, 95% CI: 0.97-1.76), with the magnitude of association somewhat stronger for lung cancer with COPD (OR=1.28, 95% CI: 0.84-1.97) than without COPD (OR=1.16, 95% CI: 0.72-1.88).
Our preliminary results provide minimal evidence of pleiotropic associations of identified genetic variants for COPD with lung cancer risk, although analyses are limited by the number of lung cancer patients examined.