Obesity promotes breast epithelium DNA damage in women carrying a germline mutation in BRCA1 or BRCA2.

ABSTRACT: Obesity, defined as a body mass index (BMI) ≥ 30, is an established risk factor for breast cancer among women in the general population after menopause. Whether elevated BMI is a risk factor for women with a germline mutation in BRCA1 or BRCA2 is less clear because of inconsistent findings from epidemiological studies and a lack of mechanistic studies in this population. Here, we show that DNA damage in normal breast epithelia of women carrying a BRCA mutation is positively correlated with BMI and with biomarkers of metabolic dysfunction. In addition, RNA sequencing showed obesity-associated alterations to the breast adipose microenvironment of BRCA mutation carriers, including activation of estrogen biosynthesis, which affected neighboring breast epithelial cel

SUBMITTER: Bhardwaj P 

PROVIDER: S-EPMC10557057 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature