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Updated: May 18, 2026

Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
Published on: October 10, 2025
Predictors of survival in never-smokers with non-small cell lung cancer: a large-scale, two-phase genetic study
Xia Pu1, Yuanqing Ye, Margaret R Spitz
1Department of Epidemiology, Thoracic/Head & Neck Medical Oncology, and Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
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.
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