Abstract 1662: Pleiotropic effects on lung cancer of genetic susceptibility variants identified for other malignancies: The Population Architecture using Genomics and Epidemiology Study
Authors: Fesinmeyer Megan D. , Lin Yi , Biggs Mary Lou , Bush William S. , Butler Anne M. , Buyske Steven , Caberto Christian P. , Carty Cara L. , Cote Michele L. , Crawford Dana C. , Dumitrescu Logan , Fowke Jay H. , Giovino Gary A. , Haiman Christopher A. , Heiss Gerardo , Hindorff Lucia A. , Kooperberg Charles , Love Shelly-Ann , Matise Tara C. , North Kari E. , Park Sungshim Lani , Peters Ulrike , Wilkens Lynne R. , Wise Anastasia L. , Marchand Loic Le , Cheng Iona C. 
Published: August 2012

Genome-wide association studies of cancer have succeeded in identifying over 100 susceptibility loci, including some, such as those found at chromosome 8q24 and CPTM1L-TERT that influence the risk of several malignancies. As part of the Population Architecture using Genomics and Epidemiology (PAGE) Study, we evaluated whether established risk variants for 18 different cancer sites, excluding the lung, impact the risk of lung cancer. A total of 152 risk variants for these 18 malignancies were selected from genome-wide association studies of cancer published through May, 2009. These SNPs were genotyped in lung cancer case-control studies of the Atherosclerosis Risk in Communities (ARIC; cases/controls=297/3088), Epidemiologic Architecture for Genes Linked to Environment (EAGLE; cases/controls=432/1567), Multiethnic Cohort (MEC; cases/controls=461/9029), and the Women's Health Initiative (WHI; cases/controls=1600/5848). The total study population was comprised of 2,790 lung cancer cases and 19,532 controls of African, American Indian, Asian, European, Latino, and Pacific Islander ancestry. For each study site, unconditional logistic regression was performed to evaluate the association between SNPs and lung cancer risk, adjusting for age, sex, race/ethnicity, and smoking status. A fixed-effect meta-analysis was performed and heterogeneity across study sites was tested. Seventeen of the 152 SNPs were associated with lung cancer risk (nominal P&lt;0.05): five breast cancer SNPs, one glioma SNP, three acute lymphocytic leukemia SNPs, one melanoma SNP, one non-Hodgkin lymphoma SNP, and six prostate cancer SNPs. By chance, only eight associations would be expected for the 152 tests (152 x 0.05=8) performed, suggesting robust significant associations among the 17 associated SNPs. The top associations (P&lt;0.01) were observed for: breast cancer SNP (rs3803662 at TOX3: OR=1.13; P=1.1x10−3), prostate cancer SNP (rs7837688 at 8q24: OR=1.19; P=5.2x10−3), and melanoma SNP (rs910873 at PIGU: OR=0.79; P=5.9x10−3). No evidence of heterogeneous effects across study sites was observed. Other analyses will test for independent genetic effects among the associated loci and examine stratified effects by sex, cell-type, and smoking status. In conclusion, findings from our meta-analysis suggest that lung cancer may share genetic risk factors and common etiologic pathways with several cancer sites.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1662. doi:1538-7445.AM2012-1662