Journal
CLINICAL CANCER RESEARCH
Volume 18, Issue 21, Pages 5983-5991Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-12-0774
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Funding
- National Cancer Institute [R01 CA111646, P50 CA070907, R01 CA055769]
- NIH through MD Anderson's Cancer Center Support Grant [CA016672]
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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 (SNP) in 904 inflammation-related genes were genotyped, and their associations with overall survival in 411 patients with LCINS at MD Anderson Cancer Center were analyzed. Next, validation of the top 27 SNPs in 311 patients with LCINS at Mayo Clinic was conducted. Results: Three SNPs (IL17RA:rs879576, BMP8A:rs698141, and STY:rs290229) were 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 the 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 with 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 biologic insight into these outcomes. Clin Cancer Res; 18(21); 5983-91. (C) 2012 AACR.
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