An international study jointly led by scientists at the University of Cambridge and Sapienza University of Rome has identified genetic factors which can increase or decrease the risk of developing breast and prostate cancer in men carrying faults in the BRCA1 and BRCA2 genes. The research can be used to inform prevention and screening strategies in these men.
Breast cancer is commonly considered a female disease with 50,000 women diagnosed annually in the UK. However, men can also develop breast cancer, with about 350 cases diagnosed annually. Breast and prostate cancer are more common in men who carry faulty versions of the BRCA genes. For example, on average 10% of men carrying a faulty BRCA2 gene will develop breast cancer and 40% will develop prostate cancer by age 80.
The team, including Drs Julie Lecarpentier, Antonis Antoniou and Professor Douglas Easton from the University of Cambridge, carried out a genome-wide association study in more than 1800 men with faults in the BRCA1 and BRCA2 genes to identify other sections in the DNA which could impact on the cancer risks associated with BRCA1 and BRCA2. The scientists found that genetic alterations in some regions which are already known to influence breast cancer risk for women and prostate cancer risk in the population at large could also modify the breast and prostate cancer risks for men carrying faults in the BRCA genes. Different combinations of these genetic alterations can increase or decrease cancer risks of developing male breast or prostate cancer from faults in the BRCA genes.
For example, they found that a man with a BRCA2 fault and most of the genetic alterations linked to the risk of developing prostate cancer has about a 60 per cent likelihood of developing prostate cancer by the time he is 80. In contrast, a man without most of these alterations has a risk of about 19 per cent. For breast cancer, the risk of developing the disease for a man with a BRCA2 fault ranges from over 14 per cent for men with most of the alterations linked to breast cancer compared to less than 5 per cent for those without most of these alterations.
In clinical practice, this stratification could allow each man to be monitored according to their own personal level of risk.
Dr Antoniou, senior author on the study and coordinator of the international study at the University of Cambridge, said “The implications of this study for early prevention and diagnosis are significant and respond to the increasing demands for personalized care for which it is essential to improve the effectiveness of the screening currently offered.”
Prof Easton, principal investigator of the EMBRACE study of women and men with faults in the BRCA genes, said “this study confirms that genetic factors for breast and prostate cancer are also important in men with BRCA faults. We now need to understand more about how these genetic alterations combine to cause an increased risk of cancers, which may lead to better approaches to preventing or treating the disease.”
Prediction of breast and prostate cancer risk in male BRCA1 and BRCA2 mutation carriers using Polygenic Risk Scores, DOI: 10.1200 / JCO. 2016.69.4935 Journal of Clinical Oncology