University of California San Francisco
UCSF School of Medicine UCSF Medical Center

Immune-mediated genetic pathways resulting in pulmonary function impairment increase lung cancer susceptibility.

Nature communications
2020
https://researcherprofiles.org/profile/87211764
31911640
Kachuri L, Johansson M, Rashkin SR, Graff RE, Bossé Y, Manem V, Caporaso NE, Landi MT, Christiani DC, Vineis P, Liu G, Scelo G, Zaridze D, Shete SS, Albanes D, Aldrich MC, Tardón A, Rennert G, Chen C, Goodman GE, Doherty JA, Bickeböller H, Field JK, Davies MP, Dawn Teare M, 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
Abstract

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 (FEV: r = 0.098, p = 2.3 × 10) and the ratio of FEV to forced vital capacity (FEV/FVC: r = 0.137, p = 2.0 × 10). Mendelian randomization analyses demonstrate that reduced FEV increases squamous cell carcinoma risk (odds ratio (OR) = 1.51, 95% confidence intervals: 1.21-1.88), while reduced FEV/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.

Journal Issue
Volume 11 of Issue 1