Document Type

Article

Publication Date

7-2-2019

Comments

This article has been peer reviewed. It is the authors' final version prior to publication in European Urology Oncology, July 2019.

The published version is available at https://doi.org/10.1016/j.euo.2019.06.010. Copyright © Chandrasekar et al.

Abstract

BACKGROUND: Prostate cancer (PCa) is increasingly recognized as part of hereditary cancer syndromes (HCSs). HCS prevalence among diverse probands seeking genetic evaluation with PCa family history (FHx) has not been reported and has implications for cascade genetic testing.

OBJECTIVE: To evaluate the rates of HCSs among probands reporting PCa FHx and germline mutations among probands.

DESIGN, SETTING, AND PARTICIPANTS: A prospective genetic testing database queried for individuals with PCa FHx. Pedigrees analyzed for three HCSs: hereditary breast and ovarian cancer (HBOC), hereditary PCa, and Lynch syndrome.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Associations between HCS overall, and with plausible link to PCA FHx and race evaluated using Fisher's exact test. Germline mutation rates described among probands with a suspicion of an HCS connected with PCa FHx.

RESULTS AND LIMITATIONS: A total of 345 probands reported PCa FHx: 53 African American (AA) and 292 Caucasian (Wh). Overall, 220 probands (63.8%) met the criteria for at least one HCS with a potential link to PCa FHx (75.5% AA; 61.6% Wh). HBOC linked to PCa FHx was identified in a higher percentage of AA than Wh probands (90.2% vs 74.6%, p=0.04). Among probands who underwent genetic testing with any HCS potentially linked to PCa FHx (n=169), 19.5% had germline mutations identified; five AA probands had germline mutations (all in BRCA1/2), while 28 Wh probands had mutations in a spectrum of genes.

CONCLUSIONS: A significant percentage of AA probands with PCa FHx meet the criteria for HCSs, with HBOC identified at the highest rate. Although limited in sample size, our findings implicate BRCA mutations in AA families with HCSs linked with PCa, underscoring the need for greater enrollment of AA participants in genetic studies.

PATIENT SUMMARY: Hereditary cancer syndromes potentially linked to prostate cancer are common in patients reporting a family history of prostate cancer. African-American patients may need special attention with regard to testing for hereditary breast and ovarian cancer syndrome, which may impact men with prostate cancer in these families.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

PubMed ID

31278035

Language

English

Available for download on Thursday, July 02, 2020

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