| Title: |
Immune-mediated genetic pathways resulting in pulmonary function impairment increase lung cancer susceptibility |
| Authors: |
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 |
| Publisher Information: |
Nature Research (part of Springer Nature) |
| Publication Year: |
2019 |
| Collection: |
Imperial College London: Spiral |
| Subject Geographic: |
England |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
Nature Communications; http://hdl.handle.net/10044/1/76382 |
| DOI: |
10.1038/s41467-019-13855-2 |
| Availability: |
http://hdl.handle.net/10044/1/76382; https://doi.org/10.1038/s41467-019-13855-2 |
| Rights: |
© The Author(s) 2020. This article is licensed under a Creative CommonsAttribution 4.0 International License, which permits use, sharing,adaptation, distribution and reproduction in any medium or format, as long as you giveappropriate credit to the original author(s) and the source, provide a link to the CreativeCommons license, and indicate if changes were made. The images or other third partymaterial in this article are included in the article’s Creative Commons license, unlessindicated otherwise in a credit line to the material. If material is not included in thearticle’s Creative Commons license and your intended use is not permitted by statutoryregulation or exceeds the permitted use, you will need to obtain permission directly fromthe copyright holder. To view a copy of this license, visithttp://creativecommons.org/licenses/by/4.0/. |
| Accession Number: |
edsbas.AA4A90C7 |
| Database: |
BASE |