Prognostic significance of genetic polymorphisms on prostate-specific antigen recurrence after a radical prostatectomy

Abstract: Approximately one-third of patients with prostate cancer show prostate-specific antigen (PSA) recurrence (biochemical failure) after a radical prostatectomy and are prone to developing metastasis with significant mortality. Although several clinicopathologic indicators, such as the PSA level, Gleason score, pathologic stage, and surgical-margin status, are used to predict outcomes after a curative-intended radical prostatectomy for localized prostate cancer, new biomarkers are still required to improve the prognosis and plan appropriate adjuvant therapy, particularly for patients at high risk of recurrence. DNA-based genetic biomarkers have several advantages over clinicopathologic indicators because they can be preoperatively examined, are easily evaluated, and can be interpreted more objectively without individual bias. In this study, the literature was reviewed from the PubMed database using the keywords “genetic polymorphisms” and “radical prostatectomy” from 1985 to April 2011. The results showed that genetic variants discovered from genome-wide association studies (such as rs1447295, rs1447295, rs6983561, rs13254738, Broad11934905, rs6983267, and rs7000448 at 8q24, rs7920517 and rs10993994 at 10q11, rs10486567 in the 7JAZF1, rs198977 in the KLK2, rs9282861 in the SULT1A1, and rs1536889 in the TLR4 gene) and single-nucleotide polymorphisms (SNPs) in important pathways (RUNX1, FGFR4, EGFR, VEGF, TNFRSF11B, vitamin D receptor, p53, WNT, inflammatory, androgen synthesis, and metabolism pathways) on prostate cancer occurrence and progression could serve as biomarkers to predict PSA recurrence after a radical prostatectomy. Including the genetic information might improve predictions of PSA recurrence after a radical prostatectomy. Future studies can be dedicated to confirming these findings in other ethnic cohorts and clarifying the roles of these SNPs/genes in the course of prostate cancer progression after a radical prostatectomy through functional analyses. [Copyright &y& Elsevier]