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Int. J. Mol. Sci. 2016, 17(12), 1970; doi:10.3390/ijms17121970

Inherited Variants in Wnt Pathway Genes Influence Outcomes of Prostate Cancer Patients Receiving Androgen Deprivation Therapy

1
Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
2
Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung 812, Taiwan
3
Department of Urology, E-Da Hospital, Kaohsiung 824, Taiwan
4
School of Medicine for International Students, I-Shou University, Kaohsiung 840, Taiwan
5
Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan
6
Department of Urology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan
7
Department of Pharmacy, Tajen University, Pingtung 907, Taiwan
8
Department of Urology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 100, Taiwan
9
Department of Urology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu 300, Taiwan
10
Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
11
Department of Pathology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
12
Department of Occupational Safety and Health, China Medical University, Taichung 404, Taiwan
13
Department of Pharmacy, China Medical University, Taichung 404, Taiwan
14
Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
15
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
16
Sex Hormone Research Center, China Medical University Hospital, Taichung 404, Taiwan
17
Department of Nursing, Asia University, Taichung 413, Taiwan
*
Authors to whom correspondence should be addressed.
Academic Editor: Carsten Stephan
Received: 26 September 2016 / Revised: 17 November 2016 / Accepted: 21 November 2016 / Published: 26 November 2016
(This article belongs to the Special Issue Diagnostic, Prognostic and Predictive Biomarkers in Prostate Cancer)
View Full-Text   |   Download PDF [1285 KB, uploaded 26 November 2016]   |  

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. View Full-Text
Keywords: prostate cancer; androgen deprivation therapy; outcomes; genetic variation; Wnt pathway prostate cancer; androgen deprivation therapy; outcomes; genetic variation; Wnt pathway
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MDPI and ACS Style

Geng, J.-H.; Lin, V.C.; Yu, C.-C.; Huang, C.-Y.; Yin, H.-L.; Chang, T.-Y.; Lu, T.-L.; Huang, S.-P.; Bao, B.-Y. Inherited Variants in Wnt Pathway Genes Influence Outcomes of Prostate Cancer Patients Receiving Androgen Deprivation Therapy. Int. J. Mol. Sci. 2016, 17, 1970.

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