Variants in inflammation genes are implicated in risk of lung cancer in never smokers exposed to second-hand smoke. Cancer Discov 2011 Oct;1(5):420-9
Date
05/16/2012Pubmed ID
22586632Pubmed Central ID
PMC3919666DOI
10.1158/2159-8290.CD-11-0080Scopus ID
2-s2.0-84863575098 (requires institutional sign-in at Scopus site) 34 CitationsAbstract
Lung cancer in lifetime never smokers is distinct from that in smokers, but the role of separate or overlapping carcinogenic pathways has not been explored. We therefore evaluated a comprehensive panel of 11,737 single-nucleotide polymorphisms (SNP) in inflammatory-pathway genes in a discovery phase (451 lung cancer cases, 508 controls from Texas). SNPs that were significant were evaluated in a second external population (303 cases, 311 controls from the Mayo Clinic). An intronic SNP in the ACVR1B gene, rs12809597, was replicated with significance and restricted to those reporting adult exposure to environmental tobacco smoke. Another promising candidate was an SNP in NR4A1, although the replication OR did not achieve statistical significance. ACVR1B belongs to the TGFR-β superfamily, contributing to resolution of inflammation and initiation of airway remodeling. An inflammatory microenvironment (second-hand smoking, asthma, or hay fever) is necessary for risk from these gene variants to be expressed. These findings require further replication, followed by targeted resequencing, and functional validation.
Author List
Spitz MR, Gorlov IP, Amos CI, Dong Q, Chen W, Etzel CJ, Gorlova OY, Chang DW, Pu X, Zhang D, Wang L, Cunningham JM, Yang P, Wu XMESH terms used to index this publication - Major topics in bold
Activin Receptors, Type IAdenocarcinoma
Airway Remodeling
Carcinoma, Non-Small-Cell Lung
Case-Control Studies
Cocarcinogenesis
Female
Genetic Predisposition to Disease
Genetic Variation
Genotype
Humans
Inflammation
Lung Neoplasms
Male
Middle Aged
Nuclear Receptor Subfamily 4, Group A, Member 1
Polymorphism, Single Nucleotide
Risk Factors
Tobacco Smoke Pollution
