Novel Method Analyzes Genetic Variations in Families with High Incidence of Breast Cancer

Hereditary or familial breast cancer accounts for about 15% of all breast cancer cases. Mutations in well-known genes such as BRCA1 and BRCA2 have been associated with an increased risk of familial breast and ovarian cancer, but these genes only explain 30-40% of familial cases. This leaves a significant number of cases with unclear genetic origins, particularly in families with a history of the disease across multiple generations. Despite this, many familial cases remain genetically unexplained due to the complex nature of the genetic factors involved. Now, a study has provided new insights into the genetic causes of familial breast cancer, particularly in families of Middle Eastern descent.

Researchers at The Hebrew University of Jerusalem (Jerusalem, Israel) conducted the study using an advanced method to examine genetic variations in families with a history of breast cancer. This approach combines machine learning with in-depth analysis of protein structures to investigate rare genetic variants. By performing whole genome sequencing and applying AI analysis, the researchers studied genetic variations in women from Middle Eastern families. The study identified significant genetic changes, connecting specific gene subgroups to critical cellular pathways involving peroxisomes, which are involved in fat metabolism. The analysis of 1218 genetic variants from 12 families revealed 80 genes that could have a significant impact on breast cancer risk. Among these, 70 genes had not been previously linked to breast cancer, greatly enhancing our understanding of the disease's genetic basis.

The study, published in Briefings in Bioinformatics, highlighted the importance of certain cellular pathways, particularly those involving peroxisomes and mitochondria, in increasing susceptibility to breast cancer and influencing patient survival. These pathways were particularly relevant across a variety of ethnic groups in seven of the studied families, emphasizing the broader significance of the findings. These discoveries open new possibilities for genetic testing and the development of targeted therapies, which could greatly improve breast cancer management and treatment across diverse populations. Furthermore, these findings may eventually lead to the creation of a specialized genetic testing panel for these groups, improving early detection and personalized treatment strategies as research continues.

"Our research not only sheds light on the elusive genetic factors behind familial breast cancer but also heralds the possibility of new, targeted treatment strategies that could eventually benefit a wider array of patients, particularly those from underrepresented groups," said Prof. Dina Schneidman-Duhovny from the Rachel and Selim Benin School of Computer Science and Engineering at the Hebrew University of Jerusalem who led the study.