Journal Article

DKFZ-2025-00956

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Genome-wide association study for lung cancer in 6531 African Americans reveals new susceptibility loci.

Byun, J. ; Han, Y. ; Choi, J. ; Sun, R. ; Shaw, V. R. ; Zhu, C. ; Xiao, X. ; Lusk, C. ; Badr, H. ; Lee, H.-S. ; Jang, H.-J. ; Li, Y. ; Lim, H. ; Long, E. ; Liu, Y. ; Kachuri, L. ; Walsh, K. M. ; Wiencke, J. K. ; Albanes, D. ; Lam, S. ; Tardon, A. ; Neuhouser, M. L. ; Barnett, M. J. ; Chen, C. ; Bojesen, S. ; Brenner, H.DKFZ* ; Landi, M. T. ; Johansson, M. ; Risch, A.DKFZ* ; Wichmann, H.-E. ; Bickeböller, H. ; Christiani, D. C. ; Rennert, G. ; Arnold, S. ; Field, J. K. ; Shete, S. ; Le Marchand, L. ; Liu, G. ; Andrew, A. S. ; Zienolddiny, S. ; Grankvist, K. ; Johansson, M. ; Caporaso, N. ; Taylor, F. ; Lazarus, P. ; Schabath, M. B. ; Aldrich, M. C. ; Patel, A. ; Lin, X. ; Zanetti, K. A. ; Harris, C. C. ; Chanock, S. ; McKay, J. ; Schwartz, A. G. ; Hung, R. J. ; Amos, C. I. ; Consortium, I.-I. (Collaboration Author)

2025
Oxford Univ. Press Oxford

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Please use a persistent id in citations: doi:10.1093/hmg/ddaf059

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.

Keyword(s): African American ; Genome-wide association study ; Lung cancer ; Polygenic risk score ; Post-GWAS

Note: Volume 34, Issue 14, 15 July 2025, Pages 1227–1237

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Contributing Institute(s):

1. C070 Klinische Epidemiologie der Krebsfrüherkennung (C070)
2. Primäre Krebsprävention (C120)
3. DKTK HD zentral (HD01)
4. Epigenomik (B370)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2025

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Essential Science Indicators ; IF < 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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