RGD Reference Report - Variants in inflammation genes are implicated in risk of lung cancer in never smokers exposed to second-hand smoke. - Rat Genome Database

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Variants in inflammation genes are implicated in risk of lung cancer in never smokers exposed to second-hand smoke.

Authors: Spitz, Margaret R  Gorlov, Ivan P  Amos, Christopher I  Dong, Qiong  Chen, Wei  Etzel, Carol J  Gorlova, Olga Y  Chang, David W  Pu, Xia  Zhang, Di  Wang, Liang  Cunningham, Julie M  Yang, Ping  Wu, Xifeng 
Citation: Spitz MR, etal., Cancer Discov. 2011 Oct;1(5):420-9. doi: 10.1158/2159-8290.CD-11-0080. Epub 2011 Aug 25.
RGD ID: 151665491
Pubmed: PMID:22586632   (View Abstract at PubMed)
PMCID: PMC3919666   (View Article at PubMed Central)
DOI: DOI:10.1158/2159-8290.CD-11-0080   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
lung non-small cell carcinoma susceptibilityIAGP 151665491DNA:SNP:intron:rs12809597(human)RGD 
lung non-small cell carcinoma susceptibilityISOACVR1B (Homo sapiens)151665491; 151665491DNA:SNP:intron:rs12809597(human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Acvr1b  (activin A receptor type 1B)

Genes (Mus musculus)
Acvr1b  (activin A receptor, type 1B)

Genes (Homo sapiens)
ACVR1B  (activin A receptor type 1B)


Additional Information