Ricerc@Sapienza

Breast cancer (BC) in men is a rare disease, whose etiology appears to be largely associated with genetic risk factors. Inherited germ-line mutations in known susceptibility genes, such as BRCA1/2 and PALB2 account for about 15% of all male BCs (MBCs). Currently, more than 25 genes have been associated with familial BC in women, most of them being involved in DNA repair and genome maintenance pathways connected with BRCA1 and BRCA2. Little is known about these emerging genes, or other genes involved in genetic syndromes, in relation to increased risk of BC in men.
Next-generation sequencing (NGS) technology offers a valuable opportunity for cancer risk assessment, allowing the analysis of multiple genes simultaneously, but unexpected findings pose challenges for clinical management. As the use of gene-panel testing is becoming widespread, there is an urgent need for well-designed case-control studies in diverse populations providing reliable estimates of risk for the purpose of counseling, since for nearly all of these emerging susceptibility genes, it is currently not possible to provide accurate risk estimates.
In our ongoing extensive genomic screening by gene-panel on MBC cases, we found unexpected mutations in cancer-related genes involved in DNA repair pathway, not yet studied in relation to MBC risk.
In this project, we aim to perform a case-control study on a large series of BRCA1/2 mutation negative MBCs, by genotyping selected pathogenic variants in DNA repair genes, including ATM, BARD1, FANCM, MUTYH, NBN and RAD51D, identified through our gene-panel screening.
Results from this study are expected to add important information to the knowledge accumulating worldwide to date, in order to help evaluating more precise and robust estimates of the MBC risk associated with these mutations. Eventually, the findings may be useful in the identification of high-risk cancer families and may eventually improve clinical management of all family members.