@article{b49f3ee90c1a4cb3b128a6e7ac66bbdd,
title = "Genome-wide association study confirms lung cancer susceptibility loci on chromosomes 5p15 and 15q25 in an African-American population",
abstract = "Objectives: Genome-wide association studies (GWAS) of lung cancer have identified regions of common genetic variation with lung cancer risk in Europeans who smoke and never-smoking Asian women. This study aimed to conduct a GWAS in African Americans, who have higher rates of lung cancer despite smoking fewer cigarettes per day when compared with Caucasians. This population provides a different genetic architecture based on underlying African ancestry allowing the identification of new regions and exploration of known regions for finer mapping. Materials and methods: We genotyped 1,024,001 SNPs in 1737 cases and 3602 controls in stage 1, followed by a replication phase of 20 SNPs (p < 1.51 × 10-5) in an independent set of 866 cases and 796 controls in stage 2. Results and conclusion: In the combined analysis, we confirmed two loci to be associated with lung cancer that achieved the threshold of genome-wide significance: 15q25.1 marked by rs2036527 (p = 1.3 × 10-9; OR = 1.32; 95% CI = 1.20-1.44) near CHRNA5, and 5p15.33 marked by rs2853677 (p = 2.8 × 10-9; OR = 1.28; 95% CI = 1.18-1.39) near TERT. The association with rs2853677 is driven by the adenocarcinoma subtype of lung cancer (p = 1.3 × 10-8; OR = 1.37; 95% CI = 1.23-1.54). No SNPs reached genome-wide significance for either of the main effect models examining smoking - cigarettes per day and current or former smoker. Our study was powered to identify strong risk loci for lung cancer in African Americans; we confirmed results previously reported in African Americans and other populations for two loci near plausible candidate genes, CHRNA5 and TERT, on 15q25.1 and 5p15.33 respectively, are associated with lung cancer. Additional work is required to map and understand the biological underpinnings of the strong association of these loci with lung cancer risk in African Americans.",
keywords = "African Americans, Genome-wide association study, Lung neoplasms, Receptors, Cholinergic, Smoking, Telomerase",
author = "Zanetti, {Krista A.} and Zhaoming Wang and Melinda Aldrich and Amos, {Christopher I.} and Blot, {William J.} and Bowman, {Elise D.} and Laurie Burdette and Qiuyin Cai and Neil Caporaso and Chung, {Charles C.} and Gillanders, {Elizabeth M.} and Haiman, {Christopher A.} and Hansen, {Helen M.} and Henderson, {Brian E.} and Kolonel, {Laurence N.} and Marchand, {Loic Le} and Shengchao Li and McNeill, {Lorna Haughton} and Ryan, {Br{\'i}d M.} and Schwartz, {Ann G.} and Sison, {Jennette D.} and Spitz, {Margaret R.} and Margaret Tucker and Wenzlaff, {Angela S.} and Wiencke, {John K.} and Lynne Wilkens and Wrensch, {Margaret R.} and Xifeng Wu and Wei Zheng and Weiyin Zhou and David Christiani and Palmer, {Julie R.} and Penning, {Trevor M.} and Rieber, {Alyssa G.} and Lynn Rosenberg and Ruiz-Narvaez, {Edward A.} and Li Su and Anil Vachani and Yongyue Wei and Whitehead, {Alexander S.} and Chanock, {Stephen J.} and Harris, {Curtis C.}",
note = "Funding Information: Karmanos Cancer Institute at Wayne State University: NIH grants R01CA060691 , R01CA87895 , contracts N01-PC35145 and P30CA22453 , Department of Health and Human Services contract HHSN261201000028C , and the Herrick Foundation . Funding Information: Project CHURCH (Creating a Higher Understanding of Cancer Research & Community Health): University Cancer Foundation , the Duncan Family Institute through the Center for Community-Engaged Translational Research , the Ms. Regina J. Rogers Gift: Health Disparities Research Program, the Cullen Trust for Health Care Endowed Chair Funds for Health Disparities Research, the Morgan Foundation Funds for Health Disparities Research and Educational Programs, and the National Institutes of Health through MD Anderson's Cancer Center Support Grant ( CA016672 ). Funding Information: The Multiethnic Cohort Study (MEC): The MEC study, blood collection, DNA extraction and genotyping was supported by National Institutes of Health grants CA63464 , CA54281 , CA1326792 , CA164973 , CA148085 , CA138338 , CA148127 and HG004726 and a Department of Defense Breast Cancer Research Program Era of Hope Scholar Award to CAH ( W81XWH-08-1-0383 ). Funding Information: Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO): The NCI African American lung cancer GWAS was supported by the intramural research program of the National Institutes of Health, National Cancer Institute . This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health . Funding Information: Philadelphia Lung Cancer Study on Gene Environment Interactions (Plus-Gene): This work was funded by grant PA4100038714 from the Pennsylvania Department of Health , NCI R21CA156087 , and NIH-NIEHS grant P30ES013508 for the Center of Excellence in Environmental Toxicology. Funding Information: The Southern Community Cohort Study (SCCS): Funding for the SCCS research was provided by NIH grant R01CA092447 . DNA Sample preparation was conducted at the Survey and Biospecimen Shared Resources, which is supported in part by Vanderbilt-Ingram Cancer Center ( P30CA068485 ), and Dr. Melinda Aldrich{\textquoteright}s effort was supported by NIH / NCI grant K07CA172294 . Publisher Copyright: {\textcopyright} 2016.",
year = "2016",
month = aug,
day = "1",
doi = "10.1016/j.lungcan.2016.05.008",
language = "English (US)",
volume = "98",
pages = "33--42",
journal = "Lung Cancer",
issn = "0169-5002",
publisher = "Elsevier Ireland Ltd",
}