Cascade testing of men with prostate cancer in families with a spectrum of inherited cancers: Importance of attention to race.

Abstract

75 Background: Prostate cancer (PCa) is increasingly recognized as a part of hereditary cancer syndromes (HCS) with 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 has implications for CGT of men with PCa. Methods: A prospectively maintained genetic testing database at a tertiary care cancer genetics program was queried for all probands reporting a PCa FHx. Pedigrees were analyzed for three HCS linked with PCa: hereditary breast and ovarian syndrome (HBOC), classic Hereditary PCa (HPC), and Lynch syndrome (LS). Associations between HCS and race were evaluated using Fisher’s exact test. 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. Results: 345 probands met inclusion criteria: 53 African-American (AA), 292 Caucasian (Wh), 74.5% female. Proband cancer diagnoses included breast (43.2%), prostate (12.8%), pancreatic (3.8%), ovarian (3.2%), and colorectal (2.9%). Overall, 63.8% of probands met criteria for ≥ 1 HCS based on personal and FHx. 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). 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). BRCA1/2 mutations accounted for all mutations identified in AA probands and 66.7% of Wh probands. Conclusions: A significant percentage of patients who present for inherited cancer assessment report a FHx of PCa potentially linked with a HCS. Importantly, AA probands with a PCa FHx have comparable rates of HCS as Wh probands, with potentially higher rates of HBOC in AA families accounted for by BRCA mutations. Cascade testing of men with PCa in families with HCS is crucial with a need to address any race-specific barriers.