Mohn Cancer Research Laboratory

BRCA1 methylation predicts cancer risk

A new study published in JAMA Oncology (September 2022) shows that BRCA1 methylation in early embryotic life leads to increased cancer risk in the adult.

Figur som viser metylering i foster, barn og voksne
BRCA1 methylation in early embryonic life leads to increased cancer risk in the adult.
Illustration: Stian Knappskog/BioRender.com

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The BRCA1 is the gene most commonly mutated in families with inherited breast and ovarian cancer. In a recent study published in JAMA Oncology (http://doi.org/10.1001/jamaoncol.2022.3846), we found epigenetic silencing of this gene in normal tissue to be a risk factor for triple-negative breast cancer (TNBC) and high-grade serous ovarian cancer (HGSOC). These are aggressive tumor types with a poor prognosis.

In the study, we found that women with low-level mosaic methylation of BRCA1, had a 2.5-fold increased risk of TNBC and 1.8 fold increased risk of HGSOC. 

These findings may have significant implications to our understanding of how a substantial fraction of these cancers originate. Previously, we detected similar low-level mosaic methylation of BRCA1 in umbilical blood from newborns (https://www.acpjournals.org/doi/epdf/10.7326/M17-0101), indicating that such methylation may develop even before birth.

In our present study, performed in collaboration with the American Women’s Health Initiative, we found BRCA1 methylation in blood samples collected many years prior to the cancer diagnosis to be associated with an elevated risk for TNBC as well as HGSOC. For the first time, this confirms such methylation to be a cancer risk factor.