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

Linda Kachuri; Mattias Johansson; Sara R Rashkin; Rebecca E Graff; Yohan Bossé; Venkata Manem; Neil E Caporaso; Maria Teresa Landi; David C Christiani; Paolo Vineis; Geoffrey Liu; Ghislaine Scelo; David Zaridze; Sanjay S Shete; Demetrius Albanes; Melinda C Aldrich; Adonina Tardón; Gad Rennert; Chu Chen; Gary E Goodman; Jennifer A Doherty; Heike Bickeböller; John K Field; Michael P Davies; M Dawn Teare; Lambertus A Kiemeney; Stig E Bojesen; Aage Haugen; Shanbeh Zienolddiny; Stephen Lam; Loïc Le Marchand; Iona Cheng; Matthew B Schabath; Eric J Duell; Angeline S Andrew; Jonas Manjer; Philip Lazarus; Susanne Arnold; James D McKay; Nima C Emami; Matthew T Warkentin; Yonathan Brhane; Ma'en Obeidat; Richard M Martin; Caroline Relton; George Davey Smith; Philip C Haycock; Christopher I Amos; Paul Brennan; John S Witte; Rayjean J Hung

doi:10.1038/s41467-019-13855-2

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

Linda Kachuri, Mattias Johansson, Sara R Rashkin, Rebecca E Graff, Yohan Bossé, Venkata Manem, Neil E Caporaso, Maria Teresa Landi, David C Christiani, Paolo Vineis, Geoffrey Liu, Ghislaine Scelo, David Zaridze, Sanjay S Shete, Demetrius Albanes, Melinda C Aldrich, Adonina Tardón, Gad Rennert, Chu Chen, Gary E GoodmanJennifer A Doherty, Heike Bickeböller, John K Field, Michael P Davies, M Dawn Teare, Lambertus A Kiemeney, Stig E Bojesen, Aage Haugen, Shanbeh Zienolddiny, Stephen Lam, Loïc Le Marchand, Iona Cheng, Matthew B Schabath, Eric J Duell, Angeline S Andrew, Jonas Manjer, Philip Lazarus, Susanne Arnold, James D McKay, Nima C Emami, Matthew T Warkentin, Yonathan Brhane, Ma'en Obeidat, Richard M Martin, Caroline Relton, George Davey Smith, Philip C Haycock, Christopher I Amos, Paul Brennan, John S Witte, Rayjean J Hung

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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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 (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.

Originalsprog	Engelsk
Artikelnummer	27
Tidsskrift	Nature Communications
Vol/bind	11
Antal sider	14
ISSN	2041-1723
DOI	https://doi.org/10.1038/s41467-019-13855-2
Status	Udgivet - 2020

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10.1038/s41467-019-13855-2Licens: CC BY

s41467-019-13855-2Forlagets udgivne version, 1,69 MBLicens: CC BY

Citationsformater

Kachuri, L., Johansson, M., Rashkin, S. R., Graff, R. E., Bossé, Y., Manem, V., Caporaso, N. E., Landi, M. T., Christiani, D. C., Vineis, P., Liu, G., Scelo, G., Zaridze, D., Shete, S. S., Albanes, D., Aldrich, M. C., Tardón, A., Rennert, G., Chen, C., ... Hung, R. J. (2020). Immune-mediated genetic pathways resulting in pulmonary function impairment increase lung cancer susceptibility. Nature Communications, 11, [27]. https://doi.org/10.1038/s41467-019-13855-2

Immune-mediated genetic pathways resulting in pulmonary function impairment increase lung cancer susceptibility. / Kachuri, Linda; Johansson, Mattias; Rashkin, Sara R; Graff, Rebecca E; Bossé, Yohan; Manem, Venkata; Caporaso, Neil E; Landi, Maria Teresa; Christiani, David C; Vineis, Paolo; Liu, Geoffrey; Scelo, Ghislaine; Zaridze, David; Shete, Sanjay S; Albanes, Demetrius; Aldrich, Melinda C; Tardón, Adonina; Rennert, Gad; Chen, Chu; Goodman, Gary E; Doherty, Jennifer A; Bickeböller, Heike; Field, John K; Davies, Michael P; Dawn Teare, M; Kiemeney, Lambertus A; Bojesen, Stig E; Haugen, Aage; Zienolddiny, Shanbeh; Lam, Stephen; Le Marchand, Loïc; Cheng, Iona; Schabath, Matthew B; Duell, Eric J; Andrew, Angeline S; Manjer, Jonas; Lazarus, Philip; Arnold, Susanne; McKay, James D; Emami, Nima C; Warkentin, Matthew T; Brhane, Yonathan; Obeidat, Ma'en; Martin, Richard M; Relton, Caroline; Davey Smith, George; Haycock, Philip C; Amos, Christopher I; Brennan, Paul; Witte, John S; Hung, Rayjean J.

I: Nature Communications, Bind 11, 27, 2020.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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 2020, 'Immune-mediated genetic pathways resulting in pulmonary function impairment increase lung cancer susceptibility', Nature Communications, bind 11, 27. https://doi.org/10.1038/s41467-019-13855-2

Kachuri, Linda ; Johansson, Mattias ; Rashkin, Sara R ; Graff, Rebecca E ; Bossé, Yohan ; Manem, Venkata ; Caporaso, Neil E ; Landi, Maria Teresa ; Christiani, David C ; Vineis, Paolo ; Liu, Geoffrey ; Scelo, Ghislaine ; Zaridze, David ; Shete, Sanjay S ; Albanes, Demetrius ; Aldrich, Melinda C ; Tardón, Adonina ; Rennert, Gad ; Chen, Chu ; Goodman, Gary E ; Doherty, Jennifer A ; Bickeböller, Heike ; Field, John K ; Davies, Michael P ; Dawn Teare, M ; Kiemeney, Lambertus A ; Bojesen, Stig E ; Haugen, Aage ; Zienolddiny, Shanbeh ; Lam, Stephen ; Le Marchand, Loïc ; Cheng, Iona ; Schabath, Matthew B ; Duell, Eric J ; Andrew, Angeline S ; Manjer, Jonas ; Lazarus, Philip ; Arnold, Susanne ; McKay, James D ; Emami, Nima C ; Warkentin, Matthew T ; Brhane, Yonathan ; Obeidat, Ma'en ; Martin, Richard M ; Relton, Caroline ; Davey Smith, George ; Haycock, Philip C ; Amos, Christopher I ; Brennan, Paul ; Witte, John S ; Hung, Rayjean J. / Immune-mediated genetic pathways resulting in pulmonary function impairment increase lung cancer susceptibility. I: Nature Communications. 2020 ; Bind 11.

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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 (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.",

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AU - Kachuri, Linda

AU - Johansson, Mattias

AU - Rashkin, Sara R

AU - Graff, Rebecca E

AU - Bossé, Yohan

AU - Manem, Venkata

AU - Caporaso, Neil E

AU - Landi, Maria Teresa

AU - Christiani, David C

AU - Vineis, Paolo

AU - Liu, Geoffrey

AU - Scelo, Ghislaine

AU - Zaridze, David

AU - Shete, Sanjay S

AU - Albanes, Demetrius

AU - Aldrich, Melinda C

AU - Tardón, Adonina

AU - Rennert, Gad

AU - Chen, Chu

AU - Goodman, Gary E

AU - Doherty, Jennifer A

AU - Bickeböller, Heike

AU - Field, John K

AU - Davies, Michael P

AU - Dawn Teare, M

AU - Kiemeney, Lambertus A

AU - Bojesen, Stig E

AU - Haugen, Aage

AU - Zienolddiny, Shanbeh

AU - Lam, Stephen

AU - Le Marchand, Loïc

AU - Cheng, Iona

AU - Schabath, Matthew B

AU - Duell, Eric J

AU - Andrew, Angeline S

AU - Manjer, Jonas

AU - Lazarus, Philip

AU - Arnold, Susanne

AU - McKay, James D

AU - Emami, Nima C

AU - Warkentin, Matthew T

AU - Brhane, Yonathan

AU - Obeidat, Ma'en

AU - Martin, Richard M

AU - Relton, Caroline

AU - Davey Smith, George

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AU - Hung, Rayjean J

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N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Female

KW - Forced Expiratory Volume

KW - Genetic Predisposition to Disease

KW - Humans

KW - Lung/physiopathology

KW - Lung Neoplasms/genetics

KW - Male

KW - Mendelian Randomization Analysis

KW - Middle Aged

KW - Phenotype

KW - Polymorphism, Single Nucleotide

KW - Prospective Studies

KW - Respiratory Function Tests

KW - Vital Capacity

U2 - 10.1038/s41467-019-13855-2

DO - 10.1038/s41467-019-13855-2

M3 - Journal article

C2 - 31911640

VL - 11

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 27

ER -