New genetic study reveals why some women get aggressive breast and ovarian cancer

In a recently published study in JAMA oncologyUniversity of Bergen researchers in collaboration with the Women’s Health Initiative (WHI) study in the US reported that epigenetic gene silencing in normal tissue is a predictive factor for triple negative breast cancer (TNBC) as well as high-grade serous ovarian cancer (HGSOC). These are aggressive types of tumors that carry a serious prognosis.

The breast cancer type 1 gene (BRCA1) is the most mutated gene in families with hereditary breast and ovarian cancer. In the study, the researchers found that women with low mosaic methylation of BRCA1 had a 2.5-fold increased risk of TNBC and a 1.8-fold increased risk of HGSOC.

Professor Lønning, the lead researcher on the study, commented: ‘These results could have important implications for our understanding of how a significant proportion of these cancers arise. We had previously found similarly low mosaic methylation of BRCA1 in neonatal cord blood, indicating that such methylation may develop before birth.

“In our current study, conducted in collaboration with the WHI, we found that BRCA1 methylation in blood samples collected many years before cancer diagnosis is associated with an increased risk of TNBC as well as HGSOC. This is confirmed for the first time that methylation is a cancer risk factor. The fact that such methylation occurs in the embryonic stage means that we need to find out why this is happening, whether it is related to environmental influences or other factors, and the provocative question arises, Whether a similar methylation may also affect other known cancer risk genes and, if so, be a triggering factor for other forms of cancer.”