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Prognostic Significance of p53 and X-ray Repair Cross-complementing Group 1 Polymorphisms on Prostate-Specific Antigen Recurrence in Prostate Cancer Post–Radical Prostatectomy

Authors' Affiliations: ¹ Department of Urology and ² Department of Family Medicine, Kaohsiung Medical University Hospital; ³ Department of Urology, Faculty of Medicine, College of Medicine, ⁴ Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, and ⁵ Graduate Institute of Occupational Safety and Health, Kaohsiung Medical University; ⁶ Department of Pathology and ⁷ Department of Surgery, Division of Urology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; and ⁸ Department of Urology, National Taiwan University College, Taipei, Taiwan

Requests for reprints: Ming-Tsang Wu, Department of Family Medicine, Kaohsiung Medical University Hospital, No. 100, Shih-Chuan 1st Road, Kaohsiung 807, Taiwan. Phone: 886-7312-1101, ext. 2315; Fax: 886-7322-1806; E-mail: 960021{at}ms.kmuh.org.tw.

Purpose: The tumor suppressor p53 and DNA repair gene X-ray repair cross-complementing group 1 (XRCC1) are thought to play important roles on prostate cancer susceptibility and tumor development. We investigated the potential prognostic roles of p53 (codon 72) and XRCC1 (codons 194, 280, and 399) polymorphisms in clinical localized prostate cancer after radical prostatectomy.

Experimental Design: A total of 126 clinical localized prostate cancer patients undergoing curative radical prostatectomy at the Kaohsiung Medical University Hospital and Kaohsiung Veterans General Hospital were included in this study. The p53 codon 72 and XRCC1 codons 194, 280 and 399 polymorphisms were determined by the PCR-RFLP method. Their prognostic significance on prostate-specific antigen (PSA) recurrence were assessed using the Kaplan-Meier analysis and Cox regression model.

Results: The p53 codon 72 Arg/Arg genotype was associated with increased PSA recurrence risk compared with the Arg/Pro and Pro/Pro genotypes, although the difference did not reach significance (30.3% versus 20.4%, P = 0.247). Of these three XRCC1 polymorphisms, the codon 399 Arg/Gln + Gln/Gn genotypes were significantly associated with higher risk of PSA recurrence after radical prostatectomy compared with the Arg/Arg genotype (34.0% versus 15.1%, P = 0.013) and poorer PSA-free survival (log-rank test, P = 0.0056). After considering for other covariates in a Cox proportional hazard model, the XRCC1 Arg/Gln and Gln/Gln genotypes (hazard ratio, 4.73; 95% confidence interval, 1.61-13.92; P = 0.005) and high Gleason score (Gleason score, 8-10; hazard ratio, 5.58; 95% confidence interval, 1.58-19.71; P = 0.008) were still independent predictors of poor PSA-free survival after radical prostatectomy. The similar significant results were not found in XRCC1 codons 194 and 280.

Conclusions: Our results suggest that the XRCC1 codon 399 polymorphism may be a prognostic factor for PSA recurrence after radical prostatectomy.