Increased risk of male cancer and identification of a potential prostate cancer cluster region in <i>BRCA2</i>

<b>Background.</b> The risk of cancer in men from <i>BRCA1</i> and <i>BRCA2</i> families is relevant to define to motivate genetic testing and optimize recommendations for surveillance. <b>Material and methods.</b> We assessed the risk of cancer in male mutation carriers and their first-degree relatives in 290 <i>BRCA1</i> and <i>BRCA2</i> families with comparison to matched controls with the aim to motivate genetic testing and optimize recommendations for surveillance. <b>Results.</b> Mutation carriers in <i>BRCA1</i> families were not at increased risk of cancer, whereas mutation carriers in <i>BRCA2</i> families were at increased risk of male breast cancer and prostate cancer with cumulative risks of 12.5% and 18.8%, respectively. Breast cancer developed at a mean age of 59 years, typically as ER/PR positive ductal carcinomas. Prostate cancer developed at a mean age of 68 years, with Gleason scores ≥ 8 in 40% of the tumors. The hazard ratio for <i>BRCA2</i>-associated prostate cancer was 3.7 (p &lt; 0.001) in mutation carriers and 3.1 (p = 0.001) in first-degree relatives. Of the 37 prostate cancers, 19 were linked to four <i>BRCA2</i> mutations within a region defined by c.6373-c.6492. Individuals with mutations herein had a HR of 3.7 for prostate cancer compared to individuals with mutations outside of this region. <b>Conclusions</b>. Male mutation carriers and first-degree relatives in <i>BRCA2</i> families are at an increased risk of breast cancer and prostate cancer with a potential prostate cancer cluster region within exon 11 of <i>BRCA2.</i>