Prognostic Significance of Prostate Cancer Susceptibility Variants on Prostate-Specific Antigen Recurrence after Radical Prostatectomy

Abstract

Recent genomewide association studies have identified several prostate cancer susceptibility variants. However, the association between these variants and biochemical failure in prostate cancer patients receiving radical prostatectomy has not been determined. We systematically evaluated 20 prostate cancer-associated single-nucleotide polymorphisms in a cohort of 320 localized prostate cancer patients receiving radical prostatectomy. Each single-nucleotide polymorphism found to be associated with the recurrence of prostate-specific antigen was further analyzed by Kaplan-Meier analysis and Cox regression model. Three prostate cancer susceptibility single-nucleotide polymorphisms (rs1447295 at 8q24, rs7920517 and rs10993994 at 10q11) were associated with prostate-specific antigen recurrence (P < 0.02). Of these, rs7920517 and rs10993994, which were in strong linkage disequilibrium (r 2 = 0.91), also showed significant associations with poor prostate-specific antigen-free survival following radical prostatectomy (log-rank test; P < 0.01). The associations remained significant in our multivariate Cox proportional hazards analysis after adjusting for other clinicopathologic risk covariates (P < 0.01). In conclusion, loci associated with risk for prostate cancer, such as rs7920517 and rs10993994, might also be used to predict the recurrence of prostate-specific antigen in prostate cancer patients receiving radical prostatectomy.

Polymorphisms inside MicroRNAs and MicroRNA Target Sites Predict Clinical Outcomes in Prostate Cancer Patients Receiving Androgen-Deprivation Therapy

“…The study population was extended from our hospitalbased prostate cancer case-control study that has been described previously (11)(12)(13)(14)(15)(16). In brief, patients with diagnosed and pathologically confirmed prostate cancer were actively recruited from 3 medical centers in Taiwan: Kaohsiung Medical University Hospital, Kaohsiung Veterans General Hospital, and National Taiwan University Hospital.…”

“…performed as described previously (14) using Sequenom iPLEX matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry technology at the National Genotyping Center, Academia Sinica, Taiwan. The average genotype call rate for these SNPs was 97.1% and the average concordance rate was 99.8% among 55 blind duplicated quality control samples.…”

The role of BRCA1 and BRCA2 in prostate cancer

“…[25][26][27] While the clinical implications of common genetic variants associated with PCa risk remain unclear, [28][29][30][31][32][33][34] deleterious germline mutations in both genes, BRCA1 and BRCA2, have been associated with more aggressive disease and poor clinical outcomes.…”

The identification of trans-associations between prostate cancer GWAS SNPs and RNA expression differences in tumor-adjacent stroma

“…However, SNPs associated with disease progression are beginning to be identified. A recent study reported that two variants at 10q11 and one variant at 8q24 associated with susceptibility influence biochemical recurrence following radical prostatectomy [49]. Variants at 8q24 have been evaluated for risks of aggressiveness of prostate cancer based on age at onset, familial aggregation and tumor grades and stages.…”