Affiliations: [a] Department of Clinical Biochemistry and Pharmacology, Soroka University Medical Center and Ben-Gurion University of the Negev, Beer-Sheva, Israel | [b] Breast Cancer Unit, Institute of Oncology, Tel Aviv University, Tel-Aviv, Israel | [c] Automated Mega-Laboratory, Tel Aviv University, Tel-Aviv, Israel | [d] Oncogenetics Unit, Sheba Medical Center, Tel Hashomer, Israel | [e] Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel
Correspondence:
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Corresponding author: Eitan Friedman, Oncogenetics Unit, Institute of Human Genetics, Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel. Tel.: +972 3 530 3173; Fax: +972 3 535 7308; E-mail: [email protected]@tauex.tau.ac.il.
Abstract: 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.
Keywords: BRCA1BRCA2 mutations, cfDNA levels, cancer risk, early detection
