Genome-wide association study for lung cancer in 6531 African Americans reveals new susceptibility loci

Despite lung cancer affecting all races and ethnicities, disparities are observed in incidence and mortality rates among different ethnic groups in the United States. Non-Hispanic African Americans had a high incidence rate of lung cancer at 55.8 per 100 000 people, as well as the highest death rate at 37.2 per 100 000 people from 2016 to 2020. While previous genome-wide association studies (GWAS) have identified over 45 susceptibility risk loci that influence lung cancer development, few GWAS have investigated the etiology of lung cancer in African Americans. To address this gap in knowledge, we conducted GWAS of lung cancer focused on studying African Americans, comprising 2267 lung cancer cases and 4264 controls. We identified three loci associated with lung cancer, one with lung adenocarcinoma, and four with lung squamous cell carcinoma in this population at the genomic-wide significance level. Among them, three novel loci were identified near VWF at 12p13.31 for overall lung cancer and GACAT3 at 2p24.3 and LMAN1L at 15q24.1 for lung squamous cell carcinoma. In addition, we confirmed previously reported risk loci with known or new lead variants near CHRNA5 at 15q25.1 and CYP2A6 at 19q13.2 associated with lung cancer and TRIP13 at 5p15.33 and ERC1 at 12p13.33 associated with lung squamous cell carcinoma. Further multi-step functional analyses shed light on biological mechanisms underlying these associations of lung cancer in this population. Our study highlights the importance of ancestry-specific studies for the potential alleviation of lung cancer burden in African Americans.

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Publication Details

Journal
Human Molecular Genetics
Published
2025-05-08
DOI
https://doi.org/10.1093/hmg/ddaf059
Citations
2
Primary Topic
RNA modifications and cancer
Type
article
Field-Weighted Citation Impact
1.61

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article

Genome-wide association study for lung cancer in 6531 African Americans reveals new susceptibility loci

Ann G. Schwartz, Alpa V Patel, Adonina Tardón, Sanjay Shete et al.
2 citations
Human Molecular Genetics
RNA modifications and cancer
1.61
article

Genome-wide association study for lung cancer in 6531 African Americans reveals new susceptibility loci

Ann G. Schwartz, Alpa V Patel, Adonina Tardón, Sanjay Shete, Shanbeh Zienolddiny, Matt J. Barnett, Stephen C. Lam, Yanhong Liu, Jinyoung Byun, Younghun Han, Angeline S. Andrew, Melinda C. Aldrich, Jiyeon Choi, Neil E. Caporaso, Catherine Zhu, John K. Wiencke, Demetrius Albanes, Angela Risch, Christopher Ian Amos, Susanne M. Arnold, Xihong Lin, Hyeyeun Lim, Mattias Johansson, Yafang Li, John K. Field, Marian L. Neuhouser, Ryan Sun, Xiangjun Xiao, Krista A. Zanetti, Curtis C. Harris, Kyle M. Walsh, Vikram R. Shaw, Loı̈c Le Marchand, Rayjean J. Hung, Hee-Jin Jang, Hoda Badr, Linda Kachuri, Christine M. Lusk, Chen Chu, Matthew B. Schabath, Heike Bickeböller, Kjell Grankvist, Hyun‐Sung Lee, Stig E. Bojesen, Hermann Brenner, Philip J. Lazarus, Gad Rennert, Maria Teresa Landi, Erping Long, James McKay, David C. Christiani, Geoffrey Liu, Mikael Johansson, Stephen J. Chanock, H‐Erich Wichmann, Fiona Taylor
article en
2 citations

Abstract

Despite lung cancer affecting all races and ethnicities, disparities are observed in incidence and mortality rates among different ethnic groups in the United States. Non-Hispanic African Americans had a high incidence rate of lung cancer at 55.8 per 100 000 people, as well as the highest death rate at 37.2 per 100 000 people from 2016 to 2020. While previous genome-wide association studies (GWAS) have identified over 45 susceptibility risk loci that influence lung cancer development, few GWAS have investigated the etiology of lung cancer in African Americans. To address this gap in knowledge, we conducted GWAS of lung cancer focused on studying African Americans, comprising 2267 lung cancer cases and 4264 controls. We identified three loci associated with lung cancer, one with lung adenocarcinoma, and four with lung squamous cell carcinoma in this population at the genomic-wide significance level. Among them, three novel loci were identified near VWF at 12p13.31 for overall lung cancer and GACAT3 at 2p24.3 and LMAN1L at 15q24.1 for lung squamous cell carcinoma. In addition, we confirmed previously reported risk loci with known or new lead variants near CHRNA5 at 15q25.1 and CYP2A6 at 19q13.2 associated with lung cancer and TRIP13 at 5p15.33 and ERC1 at 12p13.33 associated with lung squamous cell carcinoma. Further multi-step functional analyses shed light on biological mechanisms underlying these associations of lung cancer in this population. Our study highlights the importance of ancestry-specific studies for the potential alleviation of lung cancer burden in African Americans.

Human Molecular GeneticsVol. 34(14)
Dartmouth College (US), University of Hawaiʻi at Mānoa (US), University of Copenhagen (DK), American Cancer Society (US), National Institutes of Health (US), University Health Network (CA), University of Hawaii System (US), National Institute of Occupational Health (NO), 3M (United States) (US), The University of Texas MD Anderson Cancer Center (US), Harvard University (US), University of British Columbia (CA), University of Kentucky (US), University of Liverpool (GB), Universidad de Oviedo (ES), University of New Mexico (US), Washington State University Spokane (US), German Cancer Research Center (DE), University of California, San Francisco (US), Baylor College of Medicine (US), University of Salzburg (AT), University of Toronto (CA), Wayne State University (US), Chinese Academy of Medical Sciences & Peking Union Medical College (CN), Lunenfeld-Tanenbaum Research Institute (CA), Heidelberg University (DE), Markey Cancer Center (US), Copenhagen University Hospital (DK), Princess Margaret Cancer Centre (CA), Rigshospitalet (DK), Helmholtz Zentrum München (DE), Moffitt Cancer Center (US), Fred Hutch Cancer Center (US), The Barbara Ann Karmanos Cancer Institute (US), Office of the Director (US), Public Health Department (IN), Cancer Center of Hawaii (US), Sheffield Teaching Hospitals NHS Foundation Trust (GB), World Health Organization (CH), National Center for Tumor Diseases (DE), Carmel Medical Center (IL), Universitätsmedizin Göttingen (DE), Duke Medical Center (US), Division of Program Coordination Planning and Strategic Initiatives (US), German Center for Lung Research (DE), Hospital Universitario Central de Asturias (ES), National Cancer Institute (US), New Mexico Cancer Center (US), Center for Cancer Research (US), Neurological Surgery (US), Centre international de recherche sur le cancer (FR), University of Hawaii Cancer Center, UNM Comprehensive Cancer Center, Division of Cancer Epidemiology and Genetics, Epigenomics (Germany) (DE), Vanderbilt University Medical Center (US), Umeå University (SE), Stanford University (US)
National Institutes of Health
Good health and well-being
Openalex Percentile: Top 17%
RNA modifications and cancer
1.61
DOIOpen Access PDFOpenAlex
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