Male Breast Cancer (MBC) is a rare disease whose etiology appears to be largely associated with genetic factors. Inherited mutations in BRCA1 and, mainly, BRCA2, predispose to MBC and account for up to 13% of all cases in the Italian population. Furthermore, there are evidence supporting an association between increased MBC risk and pathogenic variants in PALB2, CHEK2 and ATM. Thus, additional genes that may contribute to MBC genetic susceptibility need to be investigated. In our previous extensive genomic screening by Next Generation Sequencing on a large series of MBC cases, we found germline mutations in cancer-related genes, not yet studied in relation to MBC risk.
In this project we aim to perform a large case-control study to determine the association between newly identified inherited pathogenic variants in cancer related genes and MBC risk.
Results from this study are expected to add important information to the knowledge on breast cancer (BC) risk conferred by mutations in these newly identified BC genes. This may eventually help defining more precise and robust estimates of MBC risk.
With this project we aim to better understand the genetic basis of MBC susceptibility. With the exception of BRCA1, BRCA2 and PALB2, little is known about other genes conferring susceptibility to MBC. The discovery of other rare genetic variants associated with MBC may be useful in the identification of high-risk BC families and may eventually improve clinical management of all family members, including female relatives.
To date, multi-gene panel technology is starting to enter in the routine clinical management of female BC patients. On the contrary, in MBC patients there is still an urgent need for large, well-designed case-control studies providing reliable estimates of MBC risk for the purpose of counseling.
Results from the case-control study proposed here are expected to add important information to the knowledge on BC risk conferred by mutations in these newly identified BC genes. This may help evaluating more precise and robust estimates of MBC risk.
MBC represents a good "model" to investigate the genetic component in BC susceptibility since it is not affected by confounding factors related the high frequency of the disease as for female BC, so that our results may be eventually extended to female BC, thus providing highlights in the comprehension of the missing additional genetic component of BC susceptibility in both sexes.