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.
International journal of molecular sciences. 2016 Jan 26*** epublish ***
Jiun-Hung Geng, Victor C Lin, Chia-Cheng Yu, Chao-Yuan Huang, Hsin-Ling Yin, Ta-Yuan Chang, Te-Ling Lu, Shu-Pin Huang, Bo-Ying Bao
Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. ., Department of Urology, E-Da Hospital, Kaohsiung 824, Taiwan. ., Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan. ., Department of Urology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 100, Taiwan. ., Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. ., Department of Occupational Safety and Health, China Medical University, Taichung 404, Taiwan. ., Department of Pharmacy, China Medical University, Taichung 404, Taiwan. ., Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. ., Department of Pharmacy, China Medical University, Taichung 404, Taiwan. .