Inherited variants in Wnt pathway genes influence outcomes of prostate cancer patients receiving androgen deprivation therapy
Journal
International Journal of Molecular Sciences
Journal Volume
17
Journal Issue
12
Pages
1970
Date Issued
2016
Author(s)
Abstract
Aberrant Wnt signaling has been associated with many types of cancer. However, the association of inherited Wnt pathway variants with clinical outcomes in prostate cancer patients receiving androgen deprivation therapy (ADT) has not been determined. Here, we comprehensively studied the contribution of common single nucleotide polymorphisms (SNPs) in Wnt pathway genes to the clinical outcomes of 465 advanced prostate cancer patients treated with ADT. Two SNPs, adenomatous polyposis coli (APC) rs2707765 and rs497844, were significantly (p ? 0.009 and q ? 0.043) associated with both prostate cancer progression and all-cause mortality, even after multivariate analyses and multiple testing correction. Patients with a greater number of favorable alleles had a longer time to disease progression and better overall survival during ADT (p for trend ? 0.003). Additional, cDNA array and in silico analyses of prostate cancer tissue suggested that rs2707765 affects APC expression, which in turn is correlated with tumor aggressiveness and patient prognosis. This study identifies the influence of inherited variants in the Wnt pathway on the efficacy of ADT and highlights a preclinical rationale for using APC as a prognostic marker in advanced prostate cancer. ? 2016 by the authors; licensee MDPI, Basel, Switzerland.
Subjects
Androgen deprivation therapy; Genetic variation; Outcomes; Prostate cancer; Wnt pathway
SDGs
Other Subjects
APC protein; antiandrogen; antineoplastic hormone agonists and antagonists; androgen deprivation therapy; Article; bioinformatics; cancer mortality; cancer survival; cohort analysis; controlled study; gene expression; gene mutation; genetic variation; human; human tissue; major clinical study; normal human; prostate cancer; protein expression; reverse transcription polymerase chain reaction; single nucleotide polymorphism; treatment outcome; Wnt signaling pathway; colon polyposis; disease course; drug effects; genetics; genotype; male; metabolism; pathology; physiology; prognosis; prostate; prostate tumor; Wnt signaling pathway; Adenomatous Polyposis Coli; Androgen Antagonists; Antineoplastic Agents, Hormonal; Disease Progression; Genotype; Humans; Male; Polymorphism, Single Nucleotide; Prognosis; Prostate; Prostatic Neoplasms; Wnt Signaling Pathway
Publisher
MDPI AG
Type
journal article