Predictors of survival in never-smokers with non-small cell lung cancer: A large-scale, two-phase genetic study

Xia Pu, Yuanqing Ye, Margaret R. Spitz, Liang Wang, Jian Gu, Scott M. Lippman, Michelle A T Hildebrandt, Waun Ki Hong, John D. Minna, Jack A. Roth, Ping Yang, Xifeng Wu

Research output: Contribution to journalArticle

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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 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.

Original languageEnglish (US)
Pages (from-to)5983-5991
Number of pages9
JournalClinical Cancer Research
Volume18
Issue number21
DOIs
StatePublished - Nov 1 2012

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Non-Small Cell Lung Carcinoma
Single Nucleotide Polymorphism
Lung Neoplasms
Survival
Population
Genotype
Genes
Inflammation
Research Design
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Predictors of survival in never-smokers with non-small cell lung cancer : A large-scale, two-phase genetic study. / Pu, Xia; Ye, Yuanqing; Spitz, Margaret R.; Wang, Liang; Gu, Jian; Lippman, Scott M.; Hildebrandt, Michelle A T; Hong, Waun Ki; Minna, John D.; Roth, Jack A.; Yang, Ping; Wu, Xifeng.

In: Clinical Cancer Research, Vol. 18, No. 21, 01.11.2012, p. 5983-5991.

Research output: Contribution to journalArticle

Pu, X, Ye, Y, Spitz, MR, Wang, L, Gu, J, Lippman, SM, Hildebrandt, MAT, Hong, WK, Minna, JD, Roth, JA, Yang, P & Wu, X 2012, 'Predictors of survival in never-smokers with non-small cell lung cancer: A large-scale, two-phase genetic study', Clinical Cancer Research, vol. 18, no. 21, pp. 5983-5991. https://doi.org/10.1158/1078-0432.CCR-12-0774
Pu, Xia ; Ye, Yuanqing ; Spitz, Margaret R. ; Wang, Liang ; Gu, Jian ; Lippman, Scott M. ; Hildebrandt, Michelle A T ; Hong, Waun Ki ; Minna, John D. ; Roth, Jack A. ; Yang, Ping ; Wu, Xifeng. / Predictors of survival in never-smokers with non-small cell lung cancer : A large-scale, two-phase genetic study. In: Clinical Cancer Research. 2012 ; Vol. 18, No. 21. pp. 5983-5991.
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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 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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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

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