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

Spitz, M.R., Gorlov, I.P., Amos, C.I. et al.

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 SNPs 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 a 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.

Citation

Spitz, M.R., Gorlov, I.P., Amos, C.I. et al. "Variants in inflammation genes are implicated in risk of lung cancer in never smokers exposed to second-hand smoke" Cancer Discovery (2011): 420–9