TY - JOUR
T1 - Predictors of survival in never-smokers with non-small cell lung cancer
T2 - A large-scale, two-phase genetic study
AU - Pu, Xia
AU - Ye, Yuanqing
AU - Spitz, Margaret R.
AU - Wang, Liang
AU - Gu, Jian
AU - Lippman, Scott M.
AU - Hildebrandt, Michelle A.T.
AU - Hong, Waun Ki
AU - Minna, John D.
AU - Roth, Jack A.
AU - Yang, Ping
AU - Wu, Xifeng
PY - 2012/11/1
Y1 - 2012/11/1
N2 - 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 atMD 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.
AB - 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 atMD 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.
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U2 - 10.1158/1078-0432.CCR-12-0774
DO - 10.1158/1078-0432.CCR-12-0774
M3 - Article
C2 - 22977190
AN - SCOPUS:84868545166
SN - 1078-0432
VL - 18
SP - 5983
EP - 5991
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 21
ER -