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

Cancer Biomark. 2020;28(3):269-273. doi: 10.3233/CBM-190718.


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; cancer risk; cfDNA levels; early detection.

MeSH terms

  • Adult
  • Aged
  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics
  • Biomarkers, Tumor / blood*
  • Breast / pathology
  • Breast Neoplasms / blood
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Case-Control Studies
  • Cell-Free Nucleic Acids / blood*
  • Early Detection of Cancer / methods*
  • Female
  • Germ-Line Mutation
  • Heterozygote
  • Humans
  • Liquid Biopsy
  • Middle Aged
  • Ovarian Neoplasms / blood
  • Ovarian Neoplasms / diagnosis*
  • Ovarian Neoplasms / genetics


  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Biomarkers, Tumor
  • Cell-Free Nucleic Acids