BACKGROUND: Approximately one-third of prostate cancer (PCa) patients show biochemical failure after radical prostatectomy (RP) and are prone to develop metastasis with significant mortality. Although aberrant Wnt/beta-catenin (CTNNB1) signaling has been observed in numerous types of human cancers, including PCa, to our knowledge there is currently no information on the role of Wnt signaling gene polymorphisms in PCa. METHODS: We comprehensively studied the contribution of genetic variations in CTNNB1 and adenomatous polyposis coli (APC), one of the key genes encoding the CTNNB1 destruction complex, to PCa risk and prognosis after RP using a hospital-based case-control study. We selected and genotyped 13 tagged single-nucleotide polymorphisms (tSNP) to predict common variants across entire APC and CTNNB1 genes in 307 patients with clinically localized PCa who received RP and 371 unaffected controls. RESULTS: Four tSNPs (rs3846716, rs2431238, rs41115, and rs565453) and a specific haplotype (GTAAGA) in the APC tumor suppressor gene were associated with a 0.57- to 0.71-fold lower risk of localized PCa. The association of tSNPs with prostate-specific antigen (PSA) recurrence in PCa patients was then analyzed by Kaplan-Meier analysis and Cox regression model. Interestingly, we found that the APC rs3846716 GA/AA genotypes were also significantly associated with poorer PSA-free survival (log-rank test, P = 0.037) compared with the GG genotype. CONCLUSIONS: This is the first report documenting the potential prognostic role of the APC rs3846716 GA/AA genotype on PSA recurrence after RP.
BACKGROUND: Approximately one-third of prostate cancer (PCa) patients show biochemical failure after radical prostatectomy (RP) and are prone to develop metastasis with significant mortality. Although aberrant Wnt/beta-catenin (CTNNB1) signaling has been observed in numerous types of humancancers, including PCa, to our knowledge there is currently no information on the role of Wnt signaling gene polymorphisms in PCa. METHODS: We comprehensively studied the contribution of genetic variations in CTNNB1 and adenomatous polyposis coli (APC), one of the key genes encoding the CTNNB1 destruction complex, to PCa risk and prognosis after RP using a hospital-based case-control study. We selected and genotyped 13 tagged single-nucleotide polymorphisms (tSNP) to predict common variants across entire APC and CTNNB1 genes in 307 patients with clinically localized PCa who received RP and 371 unaffected controls. RESULTS: Four tSNPs (rs3846716, rs2431238, rs41115, and rs565453) and a specific haplotype (GTAAGA) in the APC tumor suppressor gene were associated with a 0.57- to 0.71-fold lower risk of localized PCa. The association of tSNPs with prostate-specific antigen (PSA) recurrence in PCa patients was then analyzed by Kaplan-Meier analysis and Cox regression model. Interestingly, we found that the APCrs3846716 GA/AA genotypes were also significantly associated with poorer PSA-free survival (log-rank test, P = 0.037) compared with the GG genotype. CONCLUSIONS: This is the first report documenting the potential prognostic role of the APCrs3846716 GA/AA genotype on PSA recurrence after RP.
Authors: Pedro Isaacsson Velho; Wei Fu; Hao Wang; Nooshin Mirkheshti; Fahad Qazi; Fabiola A S Lima; Farah Shaukat; Michael A Carducci; Samuel R Denmeade; Channing J Paller; Mark C Markowski; Catherine H Marshall; Mario A Eisenberger; Emmanuel S Antonarakis Journal: Eur Urol Date: 2019-06-05 Impact factor: 20.096
Authors: A A Farooqi; S Mukhtar; A M Riaz; S Waseem; S Minhaj; B A Dilawar; B A Malik; A Nawaz; S Bhatti Journal: Cell Prolif Date: 2011-10-04 Impact factor: 6.831
Authors: Julienne L Carstens; Payam Shahi; Susan Van Tsang; Billie Smith; Chad J Creighton; Yiqun Zhang; Amber Seamans; Mamatha Seethammagari; Indira Vedula; Jonathan M Levitt; Michael M Ittmann; David R Rowley; David M Spencer Journal: Cancer Res Date: 2013-12-04 Impact factor: 12.701
Authors: D J Stewart; D W Chang; Y Ye; M Spitz; C Lu; X Shu; J A Wampfler; R S Marks; Y I Garces; P Yang; X Wu Journal: Pharmacogenomics J Date: 2014-07-01 Impact factor: 3.550
Authors: Thomas Van den Broeck; Steven Joniau; Liesbeth Clinckemalie; Christine Helsen; Stefan Prekovic; Lien Spans; Lorenzo Tosco; Hendrik Van Poppel; Frank Claessens Journal: Biomed Res Int Date: 2014-02-19 Impact factor: 3.411