Abstract 890: GWAS-based genetic variants and lung cancer in white postmenopausal women: The PAGE Consortium
Authors: Fesinmeyer Megan D. , Haessler Jeffrey , Carty Cara , Lin Yi , Kocarnik Jonathan D. , Kooperberg Charles , Peters Ulrike ,   PAGE Consortium
Published: June 2012

Abstract
Introduction: Lung cancer is the leading cause of cancer death in the United States, with an estimated 222,520 men and women diagnosed in 2010. While cigarette smoking is the primary causal agent in most lung cancer cases, genetic variation is known to contribute to lung cancer risk. In the present study, we aim to investigate the association between 25 single nucleotide polymorphisms (SNPs) identified in prior genome-wide association (GWA) studies of lung cancer and nicotine dependence and lung cancer in a sample of white postmenopausal women.
Methods: We selected 5,857 white subjects (1,407 cases, 4,450 controls) from the 161,808 postmenopausal women who participated in the Women's Health Initiative component of the NHGRI-funded Population Architecture using Genomics and Epidemiology (PAGE) Consortium. Lung cancer cases were identified prospectively, and confirmed via medical records review. Smoking behavior was ascertained via questionnaire at baseline. We selected 25 SNPs based on statistically significant association with either lung cancer and/or nicotine dependence in prior GWAS. We used logistic regression to estimate the association between each SNP and lung cancer assuming an additive genetic model, after adjusting for age and smoking status (current/former/never), and calculated odds ratios (OR) and 95% confidence intervals. In the subset of controls who reported any history of smoking, we used linear regression to estimate the association between each SNP and continuous pack-years of smoking.
Results: We identified nine SNPs (rs8042374, rs16969968, rs1051730, rs931794, rs8034191, rs2136100, rs578776, rs2036534, rs2836823) significantly associated with both pack-years of smoking and lung cancer adjusted for smoking status. We also identified four SNPs associated with reduced risk of lung cancer that were not significantly associated with pack-years of smoking. All four SNPs are located in CLPTM1L on Chr 5p15, a locus that has been previously associated with lung cancer in never-smokers. The A allele of rs31489 was associated with an OR of 0.79 (p = 9.03 × 10-7), the A allele of rs401681 was associated with an OR of 0.83 (p = 3.41 × 10-5), the A allele of rs402710 was associated with an OR of 0.82 (p = 5.5 × 10-5), and the G allele of rs4975616 was associated with an OR of 0.84 (p = 1.7 × 10-4).
Conclusions: These analyses confirmed prior GWAS findings of statistically significant associations between CLPTM1L and lung cancer in whites after adjustment for age and smoking status. Additional studies with larger numbers of minority lung cancer cases are needed to investigate genetic risk factors for lung cancer in non-white populations.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 890. doi:10.1158/1538-7445.AM2011-890