Association analysis of Wnt pathway genes on prostate-specific antigen recurrence after radical prostatectomy.
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.
Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Shu-Pin
SP
Huang
Wen-Chien
WC
Ting
Lu-Min
LM
Chen
Li-Chia
LC
Huang
Chia-Chu
CC
Liu
Chien-Wei
CW
Chen
Chi-Jeng
CJ
Hsieh
Wen-Hui
WH
Yang
Ta-Yuan
TY
Chang
Hong-Zin
HZ
Lee
Bo-Ying
BY
Bao
D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D000368:Aged; D016022:Case-Control Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood* / Q000235:genetics* / Q000601:surgery; D015996:Survival Rate; D016896:Treatment Outcome; D051176:beta Catenin / Q000235:genetics*
D025601:Adenomatous Polyposis Coli Protein; C495270:CTNNB1 protein, human; D051176:beta Catenin; D017430:Prostate-Specific Antigen