AUA 2019: Cascade Testing of Men with Prostate Cancer in Families with a Spectrum of Inherited Cancers: Importance of Attention to Race

Chicago, IL (UroToday.com) Prostate cancer (PCa) has long been understood to have a hereditary component – first-degree male relatives were often assessed for prostate cancer. However, as urologists, we often did not ask, nor did we recognize, the importance of other malignancies and familial syndromes in prostate cancer inheritance. However, with an increasing understanding of the genomic profile of advanced PCa and better genetic screening programs, PCa is increasingly recognized as a part of hereditary cancer syndromes (HCS), such as HBOS (Hereditary breast and ovarian syndrome), Lynch syndrome and Hereditary Prostate (HPC). These associations naturally have implications for cascade genetic testing (CGT) of men with PCa in these families. However, race-specific rates of HCS in probands presenting for inherited cancer assessment who report a family history (FHx) of PCa is not known and these results have implications for CGT of men with PCa.

To help address this question, researchers from Thomas Jefferson University’s Sidney Kimmel Cancer Center, led by Veda Giri, looked at data from a prospectively maintained genetic testing database for all tested individuals (male or female) reporting a PCa family history. Pedigrees of all probands were then analyzed for three HCS linked with PCa: hereditary breast and ovarian syndrome (HBOC), classic Hereditary PCa (HPC), and Lynch syndrome (LS). They then assessed for associations between HCS and race; beyond simple association, each HCS was evaluated for potential genetic link to the male relative with PCa and associations with race were tested using Fisher’s exact test.

345 total probands met inclusion criteria: 53 African Americans (AA) and 292 Caucasians (Wh). Full demographics are seen below:

Proband cancer diagnoses included breast (43.2%), prostate (12.8%), pancreatic (3.8%), ovarian (3.2%), and colorectal (2.9%)

First, and very importantly, 63.8% of all probands met criteria for at least one HCS based on personal and family history. This alone is important, as it is higher than would be expected – albeit, this is a highly selected population sent for genetic testing.

When specifically looking at HCS linked the family history of PCa, male relatives with PCa in these families with potential genetic link to HCS were found in 75.5% AA families and 61.6% Wh families.

HBOC was identified in a higher percentage of AA families with a potentially-linked male relative with PCa compared to Wh families (69.8% vs. 52.4%, respectively; p=0.051).

Looking at genetic mutations, among probands with HCS potentially linked to PCa (n = 169), 19.5% were found to carry a genetic mutation in a cancer risk gene (17.9% AA and 19.9% Wh). When broken down by race, BRCA1/2 mutations accounted for all mutations identified in AA probands and 66.7% of Wh pro

Based on this very interesting study, the authors draw the following conclusions:

A significant percentage of patients who present for inherited cancer assessment report a family history of PCa potentially linked with a HCS
Importantly, AA probands with a PCa FHx have comparable rates of HCS as Wh probands – but with potentially higher rates of HBOC in AA families accounted for by BRCA mutations

Ultimately, cascade testing of men with PCa in families with HCS is crucial with a need to address any race-specific barriers.

Presented by: Thenappan Chandrasekar, MD, Clinical Instructor, Thomas Jefferson University, Philadelphia, PA
Co-authors: Joon Yau Leong, Laura Gross, Sarah Hegarty, Leonard Gomella, Veda Giri, Thomas Jefferson University, Philadelphia, PA

Written by: Thenappan Chandrasekar, MD (Clinical Instructor, Thomas Jefferson University) (twitter: @tchandra_uromd, @JEFFUrology) at the American Urological Association's 2019 Annual Meeting (AUA 2019), May 3 – 6, 2019 in Chicago, Illinois

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