Faculty Collaboration Database

Predictors of survival in never-smokers with non-small cell lung cancer: a large-scale, two-phase genetic study. Clin Cancer Res 2012 Nov 01;18(21):5983-91

Date

09/15/2012

Pubmed ID

22977190

Pubmed Central ID

PMC3640870

DOI

10.1158/1078-0432.CCR-12-0774

Scopus ID

2-s2.0-84868545166 (requires institutional sign-in at Scopus site)   12 Citations

Abstract

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.

Author List

Pu X, Ye Y, Spitz MR, Wang L, Gu J, Lippman SM, Hildebrandt MA, Hong WK, Minna JD, Roth JA, Yang P, Wu X

MESH terms used to index this publication - Major topics in bold

Aged
Carcinoma, Non-Small-Cell Lung
Female
Genetic Predisposition to Disease
Humans
Inflammation
Lung Neoplasms
Male
Middle Aged
Neoplasm Staging
Polymorphism, Single Nucleotide
Prognosis
Smoking