Genetic variants of the Wnt signaling pathway as predictors of recurrence and survival in early-stage non-small cell lung cancer patients.

Angela Coscio, David W. Chang, Jack A. Roth, Yuanqing Ye, Jian Gu, Ping Yang, Xifeng Wu

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Early-stage non-small cell lung cancer (NSCLC) is potentially curative. Nevertheless, many patients will show disease recurrence after curative treatment. The Wnt signaling pathway is a developmental and stem cell pathway that plays an important role in tumorigenesis and may affect cancer progression. We hypothesize that genetic variants of the Wnt pathway may influence clinical outcome in early-stage NSCLC patients. We genotyped 441 functional and tagging single nucleotide polymorphisms (SNPs) from 54 genes of the Wnt pathway in 535 early-stage NSCLC patients treated with curative intent therapy including surgery and chemotherapy. For validation, 4 top SNPs were genotyped in 301 early-stage NSCLC patients from the Mayo Clinic. Cox proportional hazard model and combined SNP analyses were performed to identify significant SNPs correlated with recurrence-free and overall survival. Results from discovery group showed a total of 40 SNPs in 20 genes correlated with disease recurrence (P < 0.05). After correction for multiple comparisons, rs2536182 near Wnt16 remained significant (q < 0.1), which was validated in the replication population. Thirty-nine SNPs in 16 genes correlated with overall survival (P < 0.05) in the discovery group, and seven remained significant after multiple comparisons were considered (q < 0.1). In patients receiving surgery-only treatment, rs10898563 of FZD4 gene was associated with both recurrence-free and overall survival. Joint SNP analyses identified predictive markers for recurrence stratified by treatment. Our findings suggest inherited genetic variation in the Wnt signaling pathway may contribute to variable clinical outcomes for patients with early-stage NSCLC.

Original languageEnglish (US)
Pages (from-to)1284-1291
Number of pages8
JournalCarcinogenesis
Volume35
Issue number6
DOIs
StatePublished - 2014

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Wnt Signaling Pathway
Non-Small Cell Lung Carcinoma
Single Nucleotide Polymorphism
Recurrence
Survival
Genes
Therapeutics
Proportional Hazards Models
Carcinogenesis
Stem Cells
Joints
Drug Therapy
Population

ASJC Scopus subject areas

  • Cancer Research

Cite this

Genetic variants of the Wnt signaling pathway as predictors of recurrence and survival in early-stage non-small cell lung cancer patients. / Coscio, Angela; Chang, David W.; Roth, Jack A.; Ye, Yuanqing; Gu, Jian; Yang, Ping; Wu, Xifeng.

In: Carcinogenesis, Vol. 35, No. 6, 2014, p. 1284-1291.

Research output: Contribution to journalArticle

Coscio, Angela ; Chang, David W. ; Roth, Jack A. ; Ye, Yuanqing ; Gu, Jian ; Yang, Ping ; Wu, Xifeng. / Genetic variants of the Wnt signaling pathway as predictors of recurrence and survival in early-stage non-small cell lung cancer patients. In: Carcinogenesis. 2014 ; Vol. 35, No. 6. pp. 1284-1291.
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