COPD-dependent effects of genetic variation in key inflammation pathway genes on lung cancer risk.
Adult
Aged
Aged, 80 and over
Case-Control Studies
Female
Gene Regulatory Networks
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Immunity
Lung Neoplasms
/ epidemiology
Male
Middle Aged
Organ Specificity
Polymorphism, Single Nucleotide
Pulmonary Disease, Chronic Obstructive
/ complications
Young Adult
COPD
inflammation
lung cancer
targeted genetic variation
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
01 08 2020
01 08 2020
Historique:
received:
23
04
2019
revised:
10
10
2019
accepted:
21
10
2019
pubmed:
12
11
2019
medline:
12
3
2021
entrez:
12
11
2019
Statut:
ppublish
Résumé
Genome-wide association studies (GWAS) have identified several loci contributing to lung cancer and COPD risk independently; however, inflammation-related pathways likely harbor additional lung cancer risk-associated variants in biologically relevant immune genes that differ dependent on COPD. We selected single nucleotide polymorphisms (SNPs) proximal to 2,069 genes within 48 immune pathways. We modeled the contribution of these variants to lung cancer risk in a discovery sample of 1,932 lung cancer cases and controls stratified by COPD status and validation sample of 953 cases and controls also stratified by COPD. There were 43 validated SNPs in those with COPD and 60 SNPs in those without COPD associated with lung cancer risk. Furthermore, 29 of 43 and 28 of 60 SNPs demonstrated a statistically significant interaction with COPD in the pooled sample. These variants demonstrated tissue-dependent effects on proximal gene expression, enhanced network connectivity and resided together in specific immune pathways. These results reveal that key inflammatory related genes and pathways, not found in prior GWAS, impact lung cancer risk in a COPD-dependent manner. Genetic variation identified in our study supplements prior lung cancer GWAS and serves as a foundation to further interrogate risk relationships in smoking and COPD populations.
Identifiants
pubmed: 31709530
doi: 10.1002/ijc.32780
pmc: PMC7211135
mid: NIHMS1059869
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
747-756Subventions
Organisme : NCI NIH HHS
ID : P30 CA022453
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA141769
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009531
Pays : United States
Informations de copyright
© 2019 UICC.
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