Ethnic disparities among men with prostate cancer undergoing germline testing.

BACKGROUND

Prostate cancer is among the most heritable cancers, and clinical testing for germline genetic variants based on ethnicity, disease features, and family history has recently become standard of care for men with advanced disease. It is not established whether prevalence of germline variants varies based on ethnicity or race.

METHODS

We retrospectively examined germline genetic and clinical data of men reporting a diagnosis of prostate cancer referred to Color Genomics by a healthcare provider for testing of 30 genes associated with hereditary cancer risk. Variants were classified as pathogenic (P), likely pathogenic (LP), variant of uncertain significance (VUS), likely benign, or benign. P/LP and VUS prevalence was compared among subgroups classified by age at diagnosis, self-reported ethnicity, family history, and history of other cancer.

RESULTS

We identified 1,351 men reporting a diagnosis of prostate cancer of any stage who underwent germline testing. Overall, 78% of men were Caucasian, 11% Ashkenazi Jewish, 3% African-American/Canadian (AAC), 2% Hispanic, 2% Asian/Pacific Islander (API), and 4% Other (multiple, unknown, Native-American). One-hundred eighty-seven men (13.8%) carried a P/LP variant, and the most prevalent P/LP variants were in BRCA2 (3.4%), CHEK2 (2.8%), MUTYH (1.8%), and ATM (1.7%). Age at diagnosis, ethnicity, type of family member with prostate cancer, and type of second cancer were not associated with risk of carrying any P/LP variant. Ashkenazi Jewish men (6.7%) were more likely to carry P/LP BRCA2 variants than Caucasian men (2.8%) (P < 0.05). Two-hundred eighty-four men (21.0%) carried a VUS, and AAC (36.6%) and API (33.3%) men were most likely to carry a VUS (P < 0.01).

CONCLUSIONS

P/LP germline variants are prevalent in men with prostate cancer. AAC, Hispanic, and API men with prostate cancer are under-represented in studies of germline testing, potentially contributing to higher rates of VUS relative to Caucasian and Ashkenazi Jewish men. Further studies in these groups will facilitate reclassification of VUS, increasing opportunities for early detection, cancer risk modification, and targeted therapeutics.