ICARE Newsletter Summer 2016

Inherited Cancer Genes and Metastatic Prostate Cancer

Several prior studies have suggested that men with a BRCA mutation (primarily BRCA2) tend to develop an aggressive form of prostate cancer that is more likely to metastasize. These findings were recently extended through a new study published in the New England Journal of Medicine.1 In this study, almost 700 men with metastatic prostate cancer, unselected for strong family history or young age, were tested for mutations in 20 inherited cancer risk genes involved in repairing DNA damage.  Germline (inherited) mutations were identified in 82 men (11.8%), of which the most frequently mutated gene was BRCA2 (5.3%). Mutation frequency among those with metastatic prostate cancer was substantially higher than those with localized disease where only 4.6% were identified to have a mutation (p<0.001). Notably, unpublished findings presented during the 2016 American Urological Association Meeting suggested that among men with prostate cancer, BRCA mutations were significantly more common among African Americans (7.2%) compared to Caucasians (2.1%), with borderline significant results (p=0.052) of a shorter time to metastasis among African Americans. 2 Taken together, the much higher than expected frequency of inherited mutations identified among men with metastatic prostate cancer regardless of age or family history (even more so among those who are African American) in conjunction with potential relevance to targeted treatments suggest that it may be appropriate to offer genetic testing for inherited cancer genes involved in DNA repair to all men with metastatic prostate cancer.

1Pritchard CC, et al. N Engl J Med. 2016 Jul 6. PMID: 27433846.
2Petrovics G., et al.  Higher Frequency of Germline BRCA1 and BRCA2 Mutations in African American Prostate Cancer.  Presented at the 2016 American Urological Association as Abstract #MP39-18.

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