Circulating cell-free DNA (cfDNA) levels in BRCA1 and BRCA2 mutation carriers: A preliminary study

BACKGROUND: Female carriers of BRCA1 or BRCA2 germline mutations are at a substantially increased risk for developing breast and ovarian cancer. The lack of effective early detection schemes for ovarian cancer, mandate surgical removal of adnexa at age 35-40 years in these high-risk women. The role of circulating cell-free DNA (cfDNA) levels as a marker for early detection in high-risk women has rarely been reported. OBJECTIVE: To quantify cfDNA levels in BRCA1BRCA2 carriers. METHODS: Serum cfDNA levels, measured by direct fluorometric assay in cancer-free female BRCA1BRCA2 mutation carriers were compared with cancer-free controls recruited from among women undergoing breast biopsy or routine colonoscopy. RESULTS: Overall, 10 BRCA1 (185delAG) and 10 BRCA2 (6174delT) mutation carriers, 20 breast biopsy controls, and 20 colonoscopy controls participated. cfDNA levels [Median (95% CI)], were 472 (317-589) ng/ml and 525 (339-621) ng/ml in breast biopsy and colonoscopy controls, respectively. Median levels of cfDNA in BRCA1 and BRCA2 mutation carriers combined were 921 (835-1087) ng/ml, significantly higher than in both controls (P< 0.0001). CONCLUSIONS: cfDNA levels are significantly higher in BRCA1 and BRCA2 mutation carriers compared with non-carriers. This finding, if validated, may facilitate development of early detection breast/ovarian cancer biomarker in high-risk women.