title: Genetic variants of the Wnt signaling pathway as predictors of recurrence and survival in early-stage non-small cell lung cancer patients.
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.
authors: Departments of General Oncology, Epidemiology and Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA and Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors: Angela
authors: A
authors: Coscio
authors: Epidemiology and.
authors: David W
authors: DW
authors: Chang
authors: Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA and.
authors: Jack A
authors: JA
authors: Roth
authors: Epidemiology and.
authors: Yuanqing
authors: Y
authors: Ye
authors: Epidemiology and.
authors: Jian
authors: J
authors: Gu
authors: Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors: Ping
authors: P
authors: Yang
authors: Epidemiology and xwu@mdanderson.org.
authors: Xifeng
authors: X
authors: Wu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D015203:Reproducibility of Results; D012307:Risk Factors; D060449:Wnt Signaling Pathway
chemical_list: D014408:Biomarkers, Tumor