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

Intermediate magnification micrograph of a low malignant potential (LMP) mucinous ovarian tumor. H&E stain. The micrograph shows: a simple mucinous epithelium (right) and a pseudo-stratified mucinous epithelium (left – diagnosis of a PML tumor). The epithelium in a frond-like architecture is visible at the top of the image. Credit: Nephron / Wikipedia. CC BY-SA 3.0

In a recent study published in JAMA Oncology, researchers from the University of Bergen, in collaboration with the Women’s Health Initiative (WHI) study in the United States, reported that epigenetic gene silencing in normal tissues was a predictor of triple negative breast cancer (TNBC ) as well as high-grade cancer. serous ovarian cancer (HGSOC). These are aggressive types of tumors associated with a serious prognosis.

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

Professor Lønning, the investigator leading the study, commented: “These findings may have important implications for our understanding of the origin of a substantial fraction of these cancers. that such methylation can develop even before birth.

“In our current study, done in collaboration with the WHI, we found that BRCA1 methylation in blood samples taken many years before cancer diagnosis was associated with an elevated risk of TNBC as well as HGSOC. first time this confirms such that methylation is a risk factor for cancer.The fact that such methylation occurs at the embryonic stage means that we need to find out the reason why it happens, if it can be related to the influence of environment or other factors. Furthermore, it raises the provocative question whether similar methylation may also affect other known cancer risk genes and, if so, be a triggering factor for other forms of cancer.

The risk of certain cancers can be determined before birth

More information:
According to E. Lønning et al, Constitutional BRCA1 Methylation and Risk of Incident Triple-Negative Breast Cancer and High-grade Serous Ovarian Cancer, JAMA Oncology (2022). DOI: 10.1001/jamaoncol.2022.3846

Provided by the University of Bergen

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