Variants in inflammation genes are implicated in risk of lung cancer in never smokers exposed to second-hand smoke
Menée en deux phases (451 cas de cancer du poumon et 508 témoins, puis 303 cas et 311 témoins), cette étude américaine identifie des variants de gènes impliqués dans le processus inflammatoire en association avec un risque de cancer du poumon chez des non-fumeurs exposés à un tabagisme passif
Lung cancer in lifetime never smokers is distinct from that in smokers, but the role of separate or overlapping carcinogenic pathways, including inflammation, has not been comprehensively explored. We therefore evaluated a comprehensive panel of 11,737 SNPs in inflammatory-pathway genes in a discovery phase from Texas (451 lung cancer cases, 508 controls) using Illumina's Infinium iSelect Custom Genotyping. For replication (303 cases and 311 controls) from the Mayo clinic, we included all SNPs significant at p-value<0.001. An intronic SNP in the ACVR1B gene, rs12809597, was replicated with significance restricted to those reporting adult exposure to environmental tobacco smoke (OR=0.67, P=7.8x10-5). Further analysis of SNPs 1 Mb distance from this SNP suggested NR4A1 as another promising candidate, although the replication OR did not achieve statistical significance. ACVR1B belongs to the TGFR-beta superfamily, contributing to resolution of inflammation and initiation of airway remodeling after allergen challenge. We cannot exclude the etiologic role of variants in the orphan nuclear receptor NR4A1 that has an established role in the control of proliferation, apoptosis and inflammation. An inflammatory microenvironment, more likely to exist in those subjects exposed to environmental tobacco smoke, or those with asthma or hay fever, is necessary for risk from these gene variants to be expressed.
Cancer Discovery , résumé, 2011