Blood Arsenic Levels as a Marker of Breast Cancer Risk among BRCA1 Carriers

SIMPLE SUMMARY: Arsenic (As) is recognized by the International Agency for Research on Cancer (IARC) as a potent carcinogen. Numerous studies are focused on endemic regions of high exposure, and its effect on human health. Several authors suggest that As may be an important endocrine disruptor, mainly through estrogen-like activity. In our previous study on subjects without germline mutations in BRCA1, we reported that increased blood arsenic levels are significantly associated with high breast-cancer risk. The aim of this study was to assess if an association between As levels and cancer risk also exists among women harboring mutations in BRCA1. We found that women with As blood levels above the median (0.85 µg/L) had a significant 2-fold increased risk of developing breast cancer. This raises the possibility that lowering the blood arsenic level by dietary means might reduce cancer risk for BRCA1 mutation carriers. ABSTRACT: An important group of breast cancers is those associated with inherited susceptibility. In women, several predisposing mutations in genes involved in DNA repair have been discovered. Women with a germline pathogenic variant in BRCA1 have a lifetime cancer risk of 70%. As part of a larger prospective study on heavy metals, our aim was to investigate if blood arsenic levels are associated with breast cancer risk among women with inherited BRCA1 mutations. A total of 1084 participants with pathogenic variants in BRCA1 were enrolled in this study. Subjects were followed from 2011 to 2020 (mean follow-up time: 3.75 years). During that time, 90 cancers were diagnosed, including 67 breast and 10 ovarian cancers. The group was stratified into two categories (lower and higher blood As levels), divided at the median (<0.85 µg/L and ≥0.85 µg/L) As level among all unaffected participants. Cox proportional hazards models were used to model the association between As levels and cancer incidence. A high blood As level (≥0.85 µg/L) was associated with a significantly increased risk of developing breast cancer (HR = 2.05; 95%CI: 1.18–3.56; p = 0.01) and of any cancer (HR = 1.73; 95%CI: 1.09–2.74; p = 0.02). These findings suggest a possible role of environmental arsenic in the development of cancers among women with germline pathogenic variants in BRCA1.