Amos Douvdevani1, Rinat Bernstein-Molho2,3, Keren Asraf4, Ram Doolman4, Yael Laitman5, Eitan Friedman5,3. 1. Department of Clinical Biochemistry and Pharmacology, Soroka University Medical Center and Ben-Gurion University of the Negev, Beer-Sheva, Israel. 2. Breast Cancer Unit, Institute of Oncology, Tel Aviv University, Tel-Aviv, Israel. 3. Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel. 4. Automated Mega-Laboratory, Tel Aviv University, Tel-Aviv, Israel. 5. Oncogenetics Unit, Sheba Medical Center, Tel Hashomer, Israel.
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.
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.
Entities:
Keywords:
BRCA1BRCA2 mutations; cancer risk; cfDNA levels; early detection
Authors: Maha Elazezy; Katharina Prieske; Lan Kluwe; Leticia Oliveira-Ferrer; Sven Peine; Volkmar Müller; Linn Woelber; Barbara Schmalfeldt; Klaus Pantel; Simon A Joosse Journal: Mol Oncol Date: 2021-10-12 Impact factor: 6.603