Prognostic significance of cyclin D1 polymorphisms on prostate-specific antigen recurrence after radical prostatectomy.
BACKGROUND
Cyclin D1 (CCND1) is an important cell-cycle regulator involved in carcinogenesis and progression of prostate cancer. We tested whether genetic variations within the CCND1 gene are related to clinical outcomes in prostate cancer patients receiving radical prostatectomy.


METHODS
A total of 320 clinical localized prostate cancer patients who underwent radical prostatectomy in Taiwan were prospectively follow-up in this study. A total of 5 tagged single-nucleotide polymorphisms that captured the genetic variability across the CCND1 gene were genotyped, and the prognostic significance on prostate-specific antigen (PSA) recurrence was assessed using the Kaplan-Meier analysis and Cox regression model.


RESULTS
We found a polymorphism, rs9344, and 2 haplotypes, GAGG and CTGG, consisting of rs667515, rs2450254, rs9344, and rs678653, were associated with PSA recurrence (P ≤ 0.033). After adjusting for other clinicopathologic predictors, including age, PSA levels, pathologic stage, Gleason score, and surgical margin, rs9344 and the haplotype CTGG remained significant (P ≤ 0.044). The model based on clinical variables plus CCND1 rs9344 or haplotype showed improvement over the model without genetic information, as indicated by ≥ 7.2 % net reclassification improvement (P ≤ 0.040), integrated discrimination index (P ≤ 0.041), and likelihood ratio test (P ≤ 0.028).


CONCLUSIONS
Our data suggest that the CCND1 rs9344 and a specific haplotype CTGG may be prognostic factors for PSA recurrence after radical prostatectomy.
Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
Chia-Cheng
CC
Yu
Victor C
VC
Lin
Chao-Yuan
CY
Huang
Chia-Chu
CC
Liu
Jyh-Seng
JS
Wang
Tony T
TT
Wu
Yeong-Shiau
YS
Pu
Chun-Hsiung
CH
Huang
Chun-Nung
CN
Huang
Shu-Pin
SP
Huang
Bo-Ying
BY
Bao
D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D019938:Cyclin D1 / Q000235:genetics*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; 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* / Q000473:pathology / Q000601:surgery
D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; D019938:Cyclin D1; D017430:Prostate-Specific Antigen