Increased risk of male cancer and identification of a potential prostate cancer cluster region in BRCA2

Abstract

Background. The risk of cancer in men from BRCA1 and BRCA2 families is relevant to define to motivate genetic testing and optimize recommendations for surveillance.

Material and methods. We assessed the risk of cancer in male mutation carriers and their first-degree relatives in 290 BRCA1 and BRCA2 families with comparison to matched controls with the aim to motivate genetic testing and optimize recommendations for surveillance.

Results. Mutation carriers in BRCA1 families were not at increased risk of cancer, whereas mutation carriers in BRCA2 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 BRCA2-associated prostate cancer was 3.7 (p < 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 BRCA2 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.

Conclusions. Male mutation carriers and first-degree relatives in BRCA2 families are at an increased risk of breast cancer and prostate cancer with a potential prostate cancer cluster region within exon 11 of BRCA2.

Acknowledgments

We would like to acknowledge Prof. Ake Borg, Institute of Clinical Sciences, Division of Oncology and Pathology, Lund University, Sweden, Ass. Professor Mads Thomassen, Department of Clinical Genetics, Odense University Hospital, PhD Inge Søkilde Pedersen, Department of Molecular Diagnostics, Aalborg University Hospital and PhD Thomas van Overeem Hansen, Department of Genomic Medicine, Rigshospitalet, Copenhagen, Denmark for data on disease-predisposing mutations. The study was financially supported by the Aase and Einar Danielsens Fund, the Research Council, Vejle Hospital. No conflicts of interest apply for any of the authors. The authors alone are responsible for the content and writing of the paper.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Supplementary material available online

Supplementary Table I online at: http://informahealthcare.com/doi/abs/10.3109/0284186X.2015.1067714