Mutations in the BRCA1 and BRCA2 genes, even if equally inherited by both sexes, represent a relevant example of gender medicine. Their role in the susceptibility to hereditary forms of purely female neoplasms, such as breast and ovarian cancer, is well known and has routinely entered into clinical practice; on the contrary, the impact on the oncological risk of the same mutations in male subjects is less known.

A study, coordinated by Laura Ottini of the Department of Molecular Medicine of Sapienza University, in collaboration with the international consortium CIMBA (Consortium of Investigators of Modifiers of BRCA1/2), has highlighted significant and peculiar characteristics in the cancer spectrum occurring in men with BRCA1 and BRCA2 mutationsthese mutations. The outcomes of this research also supported by AIRC Foundation (Italian Foundation for Cancer Research), have been published on the prestigious scientific journal JAMA Oncology.

"Thanks to the collaboration of more than 50 research groups around the world, we have obtained and analysed clinical data of about 7000 men with BRCA1 and BRCA2 mutations" - says Valentina Silvestri of the Department of Molecular Medicine, in charge of the data analysis. "Whilst we know that the two BRCA genes have a different impact on cancer risk in women, little was known about similar differences in men. This study allowed us to compare the clinical characteristics of men with BRCA1 mutations with those of men with BRCA2 mutations in order to highlight any differences in a large number of cases, to date, the most numerous in literature."

The outcomes show that, unlike women, where BRCA1 gives a higher risk, men with BRCA2 mutations are about three times more likely to have cancer than those with BRCA1 mutations. In particular, breast, prostate and pancreatic cancers are significantly more frequent in men with BRCA2 mutations than in BRCA1, as well as more neoplasms throughout life and an earlier age of disease onset. By contrast, the cancer spectrum in men with BRCA1 mutations is more heterogeneous, with a higher frequency of colon cancer.

"These differences will have to be taken into account to improve the effectiveness of cancer screening and surveillance programmes in men with BRCA mutations," - says Laura Ottini." More broadly, the results of this study may help oncologists raise awareness among men with BRCA mutations in the way they perceive their cancer risk, and not only among their female relatives. Moreover, this data will also help guide the subsequent studies we are currently working on, in order to develop more and more gender-specific and personalised guidelines to ensure better clinical management for all patients."

References:

Characterization of the cancer spectrum in men with germline BRCA1 and BRCA2 pathogenic variants:  Results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) - Silvestri V., Leslie G., Barnes D.R., ... Ottini L. - JAMA Oncology (2020) DOI: 10.1001/jamaoncol.2020.2134

Further Information

Laura Ottini
Department of Molecular Medicine
laura.ottini@uniroma1.it