LAUSR

Key Points Question Is mosaic BRCA1 promoter methylation in normal tissue associated with the risk of incident high-grade serous ovarian cancer (HGSOC) and triple-negative breast cancer (TNBC)? Findings In this nested case-control study including 637 women developing TNBC and 511 developing HGSOC, white blood cell BRCA1 promoter methylation was associated with a significantly elevated risk of developing both cancer forms (hazard ratio for HGSOC of 1.93 and TNBC of 2.35). The results remained significant in a subgroup analysis of women who received a diagnosis of cancer more than 5 years after blood sampling (hazard ratio of 1.82 and 2.52, respectively). Meaning The study results may serve as proof of concept for early life constitutional methylation as a cancer risk factor.