Predictors of survival in never-smokers with non-small cell lung cancer: a large-scale, two-phase genetic study
A l'aide du génotypage de 11 930 polymorphismes à simple nucléotide de 904 gènes liés à l'inflammation, cette étude identifie les variants génétiques associés à la survie globale chez les patients n'ayant jamais fumé et atteints d'un cancer du poumon non à petites cellules (411 cas)
Purpose: Lung cancer in never-smokers (LCINS) is increasingly recognized as a distinct disease from that in ever-smokers owing to substantial differences in etiology, clinical characteristics, and prognosis. Therefore, we aimed to identify prognostic markers specific for LCINS. Experimental Design: First, 11,930 single-nucleotide polymorphisms (SNPs) in 904 inflammation-related genes were genotyped, and their associations with overall survival in 411 LCINS patients at MD Anderson Cancer Center were analyzed. Next, validation of the top 27 SNPs in 311 LCINS patients at Mayo Clinic was performed. Results: Three SNPs (IL17RA:rs879576, BMP8A:rs698141, and STY:rs290229) validated (p<0.05), and two SNPs (CD74:rs1056400 and CD38:rs10805347) reached borderline significance (p=0.08) in the Mayo Clinic population. We validated a survival-tree created in MD Anderson population exploring gene-gene interactions in the Mayo Clinic population. This survival-tree stratified patients into subsets with significantly different risks of death: patients with the rs1056400_GG/rs698141_GA+AA genotype had significantly higher risk of death in both MD Anderson (HR:2.32, 95%CI:1.58-3.41) and Mayo (HR:1.97, 95%CI:1.11-3.50) populations compared to those with the rs1056400_GG/rs698141_GG or rs1056400_GA+AA genotype. We evaluated these five SNPs in 996 ever-smokers from MD Anderson and found no significant associations. Conclusions: Our study provides strong evidence that inflammation-related genetic variations can affect clinical outcomes in LCINS, which may lead to significant biological insight into these outcomes.
Clinical Cancer Research , résumé, 2012