By Inka Burow,Hannover Medical School

At the MHH Institute of Human Genetics: Prof. Dr. Doris Steinemann, Dr. Bernardus Aldrige Allister and Prof. Dr Monika Golas (from left). Credit: Karin Kaiser/MHH

Breast cancer is the most common form of cancer among women in Germany: Around 1 in 8 women will develop it during their lifetime. In around 5% to 10% of cases, the condition is caused by a hereditary predisposition. Thirteen risk genes have currently been identified for genetic testing, including the BRCA1 and BRCA2 genes. Variations (mutations) in these genes are associated with a significantly increased risk of breast cancer.

A research team led by Dr. Doris Steinemann from the Institute of Human Genetics at Hannover Medical School (MHH) and Dr. Monika Golas from the Institute of Human Genetics at the University of Augsburg and Augsburg University Hospital has identified further genes and gene variants associated with an increased risk of breast cancer. The lead author is Dr. Bernardus Aldrige Allister, formerly of the MHH Institute of Human Genetics.

The results are published innpj Breast Cancer.

People who have several relatives with breast or ovarian cancer, or who have developed breast cancer at a young age or in both breasts, are at an increased risk of cancer. They can access genetic counseling and testing. The test screens fordisease-relevant variantsin the high-risk genes BRCA1 and BRCA2, as well as 11 other risk genes. A clear genetic cause can be identified in around 20% of those seeking advice. This gives them access to personalized services for early detection, risk reduction and treatment. For the remaining individuals, the cause remains unclear for the time being.

The research team led by Steinemann and Golas analyzed the complete set of genes and gene activity in blood samples from 134 people with breast or ovarian cancer, or both breast and ovarian cancer. In all of these individuals, routine testing of the 13 known cancer risk genes had previously failed to identify a genetic cause for their cancers.

"Our findings highlight the importance of additional genes that play a key role in DNA repair and genome stability, and which are therefore new candidate genes for families with suspected hereditary breast and ovarian cancer," Steinemann says.

Among the candidate genes were genes that had previously been associated primarily with rare diseases. In the case of these diseases, both copies of the gene—that is, the maternal and paternal copies—must usually be altered for the disease to develop. The study's findings suggest that alterations in just one copy of some of these genes could also increase susceptibility to breast and ovarian cancer.

"As the number ofgenome sequencing projectsincreases, it will become possible to better assess the significance of rare genetic variants—including through their inclusion in genomDE, the pilot project for comprehensive diagnostics and personalized treatment planning for rare and oncological diseases," Golas says.

Women and men with a family history of breast and/or ovarian cancer, as well as those who have been diagnosed with breast or ovarian cancer at a young age, can find support at the Centers for Familial Breast and Ovarian Cancer and their partner organizations, such as the Center for Familial Breast and Ovarian Cancer at the MHH.