Breast cancer: not only a woman’s disease

Laura Ottini, Department of Molecular Medicine
Life Sciences

Breast cancer is commonly considered a female disease. However, men can also be affected, albeit to a lesser extent. In fact, among all male tumors, breast cancer has an incidence of 1%, which is very low if compared with the 25% of prostate cancer.

Mutations in BRCA1 and BRCA2 genes predispose to develop about 15% of male breast cancer and 2% of prostate cancer. These are high-penetrance genes, it means that their alterations greatly increase the risk of being affected by cancer. It should be said, however, that not all individuals inheriting their mutations have the same risk of developing a tumor throughout their life.

Laura Ottini of the Department of Molecular Medicine, Sapienza University of Rome, in collaboration with Antonis Antoniou of the University of Cambridge and with several research groups participating in the CIMBA international consortium, showed that the risk of developing breast and prostate cancer in men with BRCA1 and BRCA2 mutations is associated with the presence of several genetic polymorphisms. Polymorphisms are variants of the single nucleotides, i.e. the units that build the DNA molecule.

Thanks to the sequencing of the entire human genome, we know that every individual has millions of polymorphisms in his genome and that some of them are associated with an increased risk of developing a tumor.

The research, which was also supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC), has taken advantage of data collected by analyzing over 500,000 polymorphisms in 1,802 men carrying mutations in BRCA1 and BRCA2. With a GWAS (Genome Wide Association Study) approach, data from affected cases were compared to those from healthy individuals, and a statistical model, the PRS (Polygenic Risk Score), was constructed with 88 polymorphisms for breast cancer and 103 for prostate cancer. The results are published in the prestigious Journal of Clinical Oncology.

In the study, made possible thanks also to the contribution of Valentina Silvestri, winner of Sapienza research grant in this field, the constructed PRS predicts the risk of developing breast and prostate cancer in men with BRCA1 and BRCA2 mutations. For example, in men with mutations in BRCA2, the overall risk of developing prostate cancer is around 40%: PRS classifies these men in low PRS individuals, ie. with a risk of about 19%, and in high PRS individuals, ie. with a risk of about 61%. In clinical practice, this stratification could allow each individual to monitor personal risk, reserving greater controls for high-risk or high PRS individuals.

"The implications of this study for early prevention and diagnosis are remarkable - says Laura Ottini - and respond to the increasing need of a personalized medicine, for which it is crucial to improve the effectiveness of currently proposed screening".


Team Leader
Laura Ottini
Dip. di Medicina molecolare
[©] Materiale aggiuntivo: