title: Inherited Variants in Wnt Pathway Genes Influence Outcomes of Prostate Cancer Patients Receiving Androgen Deprivation Therapy.
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 andq≤ 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 (pfor trend ≤ 0.003). Additional, cDNA array and in silico analyses of prostate cancer tissue suggested that rs2707765 affectsAPCexpression, 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 usingAPCas a prognostic marker in advanced prostate cancer.
authors.affiliation: Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. u9001090@hotmail.com.|Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung 812, Taiwan. u9001090@hotmail.com.
authors.forename: Jiun-Hung
authors.initials: JH
authors.lastname: Geng
authors.affiliation: Department of Urology, E-Da Hospital, Kaohsiung 824, Taiwan. victorlin0098@yahoo.com.tw.|School of Medicine for International Students, I-Shou University, Kaohsiung 840, Taiwan. victorlin0098@yahoo.com.tw.
authors.forename: Victor C
authors.initials: VC
authors.lastname: Lin
authors.affiliation: Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan. ccyu@vghks.gov.tw.|Department of Urology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan. ccyu@vghks.gov.tw.|Department of Pharmacy, Tajen University, Pingtung 907, Taiwan. ccyu@vghks.gov.tw.
authors.forename: Chia-Cheng
authors.initials: CC
authors.lastname: Yu
authors.affiliation: Department of Urology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 100, Taiwan. cyhuang0909@ntu.edu.tw.|Department of Urology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu 300, Taiwan. cyhuang0909@ntu.edu.tw.
authors.forename: Chao-Yuan
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. schoolyin@gmail.com.|Department of Pathology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. schoolyin@gmail.com.
authors.forename: Hsin-Ling
authors.initials: HL
authors.lastname: Yin
authors.affiliation: Department of Occupational Safety and Health, China Medical University, Taichung 404, Taiwan. tychang@mail.cmu.edu.tw.
authors.forename: Ta-Yuan
authors.initials: TY
authors.lastname: Chang
authors.affiliation: Department of Pharmacy, China Medical University, Taichung 404, Taiwan. lutl@mail.cmu.edu.tw.
authors.forename: Te-Ling
authors.initials: TL
authors.lastname: Lu
authors.affiliation: Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. shpihu@yahoo.com.tw.|Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. shpihu@yahoo.com.tw.|Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. shpihu@yahoo.com.tw.
authors.forename: Shu-Pin
authors.initials: SP
authors.lastname: Huang
authors.affiliation: Department of Pharmacy, China Medical University, Taichung 404, Taiwan. bao@mail.cmu.edu.tw.|Sex Hormone Research Center, China Medical University Hospital, Taichung 404, Taiwan. bao@mail.cmu.edu.tw.|Department of Nursing, Asia University, Taichung 413, Taiwan. bao@mail.cmu.edu.tw.
authors.forename: Bo-Ying
authors.initials: BY
authors.lastname: Bao
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics; D000726:Androgen Antagonists / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D018450:Disease Progression; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011467:Prostate / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000235:genetics / Q000502:physiology
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal
keywords: Wnt pathway; androgen deprivation therapy; genetic variation; outcomes; prostate cancer