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Lookup NU author(s): Professor Dawn Teare, Dr Paul Brennan
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2020, The Author(s). Impaired lung function is often caused by cigarette smoking, making it challenging to disentangle its role in lung cancer susceptibility. Investigation of the shared genetic basis of these phenotypes in the UK Biobank and International Lung Cancer Consortium (29,266 cases, 56,450 controls) shows that lung cancer is genetically correlated with reduced forced expiratory volume in one second (FEV1: rg = 0.098, p = 2.3 × 10−8) and the ratio of FEV1 to forced vital capacity (FEV1/FVC: rg = 0.137, p = 2.0 × 10−12). Mendelian randomization analyses demonstrate that reduced FEV1 increases squamous cell carcinoma risk (odds ratio (OR) = 1.51, 95% confidence intervals: 1.21–1.88), while reduced FEV1/FVC increases the risk of adenocarcinoma (OR = 1.17, 1.01–1.35) and lung cancer in never smokers (OR = 1.56, 1.05–2.30). These findings support a causal role of pulmonary impairment in lung cancer etiology. Integrative analyses reveal that pulmonary function instruments, including 73 novel variants, influence lung tissue gene expression and implicate immune-related pathways in mediating the observed effects on lung carcinogenesis.
Author(s): Kachuri L, Johansson M, Rashkin SR, Graff RE, Bosse Y, Manem V, Caporaso NE, Landi MT, Christiani DC, Vineis P, Liu G, Scelo G, Zaridze D, Shete SS, Albanes D, Aldrich MC, Tardon A, Rennert G, Chen C, Goodman GE, Doherty JA, Bickeboller H, Field JK, Davies MP, Teare MD, Kiemeney LA, Bojesen SE, Haugen A, Zienolddiny S, Lam S, Le Marchand L, Cheng I, Schabath MB, Duell EJ, Andrew AS, Manjer J, Lazarus P, Arnold S, McKay JD, Emami NC, Warkentin MT, Brhane Y, Obeidat M, Martin RM, Relton C, Davey Smith G, Haycock PC, Amos CI, Brennan P, Witte JS, Hung RJ
Publication type: Article
Publication status: Published
Journal: Nature Communications
Year: 2020
Volume: 11
Online publication date: 07/01/2020
Acceptance date: 29/11/2019
Date deposited: 20/01/2020
ISSN (electronic): 2041-1723
Publisher: Nature Publishing Group
URL: https://doi.org/10.1038/s41467-019-13855-2
DOI: 10.1038/s41467-019-13855-2
PubMed id: 31911640
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