COPD-dependent effects of genetic variation in key inflammation pathway genes on lung cancer risk.
Int J Cancer
; 147(3): 747-756, 2020 08 01.
Article
in En
| MEDLINE
| ID: mdl-31709530
ABSTRACT
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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Polymorphism, Single Nucleotide
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Pulmonary Disease, Chronic Obstructive
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Gene Regulatory Networks
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Immunity
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Lung Neoplasms
Type of study:
Etiology_studies
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Observational_studies
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Risk_factors_studies
Limits:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Language:
En
Year:
2020
Type:
Article