Mutations in the BRCA1 and BRCA2 genes predispose the development of approximately 15% of male breast cancers and 2% of prostate cancers. However, not all individuals who inherit these mutations are equally likely to develop cancer in their lifetime.

The international research team coordinated by Laura Ottini of the Department of Molecular Medicine at Sapienza University of Rome has identified new genetic polymorphisms, i.e. DNA variations that are frequent in the population, which may alter the risk of developing breast and prostate cancer in men carrying BRCA1 and BRCA2 mutations.

The results of this research carried out in collaboration with the University of Cambridge and several research groups of the international consortium CIMBA (Consortium of Investigators of Modifiers of BRCA1/2) and also supported by AIRC - Fondazione AIRC per la ricerca sul cancro, have been published in the Journal of the National Cancer Institute (JNCI). 

Using data obtained in a Genome-Wide Association Study to determine gene variations in 1,801 men carrying mutations in the BRCA1 and BRCA2 genes, researchers developed new statistical models of Polygenic Risk Scores (PRS) to include all newly discovered (genetic) factors associated with breast and prostate cancer. Specifically, the PRS developed in the study are based on 313 polymorphisms for breast cancer and 147 for prostate cancer.

By increasing the number of polymorphisms included in the PRS model based on the latest scientific evidence, it is possible to further refine the estimation of the risk of developing breast and prostate cancer in a group of men who are at high risk for these diseases and may already benefit from specific cancer screening.

"For example," says Laura Ottini, "in men carrying BRCA2 mutations, the risk of developing prostate cancer is about 60% overall: the new model makes it possible to classify these men into low PRS individuals, i.e. with a risk of about 34%, and high PRS individuals, i.e. with a risk of over 87%".

In clinical practice, this stratification could allow each individual to be monitored according to their personal risk, with individuals with higher PRS receiving more follow-up. Improving the effectiveness of currently offered screening is of paramount importance for prevention and early detection. In this sense, the study's implications are considerable and respond to the growing demands for personalised and gender-specific medicine.

References:

Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores - Daniel R Barne, Valentina Silvestri… Laura Ottini - Journal of the National Cancer Institute 2021. DOI: 10.1093/jnci/djab147.

Further Information

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