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Prostate cancer risk allele specific for African descent associates with pathologic stage at prostatectomy.

ABSTRACT: PURPOSE:A region on chromosome 8q24 was recently identified as a novel prostate cancer risk locus. Inherited variation in this region is associated with prostate cancer risk in the general population (21-58%), and specific alleles show a strong association in African-American men. This study was designed to evaluate associations between 8q24 risk alleles and clinical variables, such as pathologic stage, age at diagnosis, and recurrence, in a case series of African-American men. EXPERIMENTAL DESIGN:Peripheral blood DNA samples from 114 African-American men with prostate cancer, including 106 who had undergone radical prostatectomy, were genotyped for six single-nucleotide polymorphisms on three 8q24 regions. The presence of these single-nucleotide polymorphisms was compared with clinicopathologic and follow-up data after radical prostatectomy. RESULTS:The mean age of diagnosis and follow-up time were 57.4 (+/-8.9) years and 49.1 (+/-31.6) months, respectively. Patients carrying the Broad11934905 A risk allele, which is specific for African ancestry, were more likely to have a higher pathologic stage (pT(3-4)) than individuals with the wild type (odds ratio, 4.48; 95% confidence interval, 1.42-14.14; P = 0.011). A trend toward increased frequency of and shorter time to biochemical recurrence was noted in patients with this risk allele on Kaplan-Meier unadjusted survival analysis (P = 0.076). CONCLUSIONS:The Broad11934905 polymorphism at 8q24, which is only found in people of African ancestry, is associated with an increase in non-organ-confined prostate cancer at prostatectomy. In addition, for those with this risk allele, there is a trend toward early biochemical recurrence that requires validation in larger studies.

SUBMITTER: Whitman EJ

PROVIDER: S-EPMC6880746 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Prostate cancer risk allele specific for African descent associates with pathologic stage at prostatectomy.

Whitman Eric J EJ Pomerantz Mark M Chen Yongmei Y Chamberlin Michael M MM Furusato Bungo B Gao Chunling C Ali Amina A Ravindranath Lakshmi L Dobi Albert A Sesterhenn Isabell A IA McLeod David G DG Srivastava Shiv S Freedman Matthew M Petrovics Gyorgy G

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20100101 1

<h4>Purpose</h4>A region on chromosome 8q24 was recently identified as a novel prostate cancer risk locus. Inherited variation in this region is associated with prostate cancer risk in the general population (21-58%), and specific alleles show a strong association in African-American men. This study was designed to evaluate associations between 8q24 risk alleles and clinical variables, such as pathologic stage, age at diagnosis, and recurrence, in a case series of African-American men.<h4>Experi ...[more]

PMID: 20056617

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Project description:ImportanceWhether the conventional 1.5-month to 2.0-month time interval following radical prostatectomy (RP) for prostate cancer (PC) is sufficient to accurately document a persistent prostate-specific antigen (PSA) remains unanswered.ObjectiveTo evaluate the time necessary to accurately document a persistent PSA level after RP.Design, setting, and participantsThis cohort study evaluated whether a significant interaction existed between (1) a pre-RP PSA level greater than 20 ng/mL vs 20 ng/mL or less and (2) persistent PSA vs undetectable PSA after RP on PC-specific mortality (PCSM) risk and all-cause mortality (ACM) risk, adjusting for known PC prognostic factors, age at RP, year of RP, and the time-dependent use of post-RP radiation therapy (RT) and androgen deprivation therapy (ADT). Whether an increasing persistent PSA level was associated with a worse prognosis was also investigated. Patients with T1N0M0 to T3N0M0 PC treated with RP between 1992 and 2020 at 2 academic centers were included. Follow-up data were collected until November 2023. Data were analyzed from July 2024 to January 2025.ExposureRP.Main outcomes and measuresAdjusted hazard ratio (aHR) of ACM and PCSM risk.ResultsOf 30 461 patients included in the discovery cohort, the median (IQR) age was 64 (59-68) years; of 12 837 patients included in the validation cohort, the median (IQR) age was 59 (54-64) years. Compared with patients with undetectable PSA, among patients with persistent PSA, a pre-RP PSA level greater than 20 ng/mL vs 20 ng/mL or less was significantly associated with reduced ACM risk (aHR, 0.69; 95% CI, 0.51-0.91; P = .01; P for interaction < .001) and PCSM risk (aHR, 0.41; 95% CI, 0.25-0.66; P < .001; P for interaction = .02). This result remained after adjustment for prostate volume and was confirmed in the validation cohort for PCSM risk and may represent a higher proportion of patients with a pre-RP PSA greater than 20 ng/mL vs 20 ng/mL or less who could have reached an undetectable PSA level if additional time for PSA assessment occurred before initiating post-RP therapy for presumed persistent PSA. Notably, there was more frequent and a shorter median time to post-RP RT plus ADT or ADT use in patients with a pre-RP PSA greater than 20 ng/mL (244 of 446 [54.7%] at a median [IQR] of 2.68 [1.51-4.40] months) vs 20 ng/mL or less (338 of 972 [34.8%] at a median [IQR] of 3.30 [2.00-5.39] months). These treatment times were shorter than the times to an undetectable PSA in observed patients (median [IQR] of 2.96 [1.84-3.29] months vs 3.37 [2.35-4.09] months, respectively). Increasing persistent PSA level was associated with an increased ACM risk (aHR, 1.14; 95% CI, 1.04-1.24; P = .004) and PCSM risk (aHR, 1.27; 95% CI, 1.12-1.45; P < .001).Conclusions and relevancePSA level assessed for at least 3 months after RP may minimize overtreatment, and in this study, a higher persistent PSA level was associated with a worse prognosis.

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Prostate cancer risk allele specific for African descent associates with pathologic stage at prostatectomy.

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Prostate cancer risk allele specific for African descent associates with pathologic stage at prostatectomy.

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