BRCA1 promoter methylation in peripheral blood DNA was identified in sporadic breast cancer and controls

Cancer Epidemiol. 2012 Jun;36(3):e177-82. doi: 10.1016/j.canep.2012.02.001. Epub 2012 Mar 7.


Objective: Epigenetics, particularly DNA methylation, has recently been shown to be important in breast cancer initiation. We investigated the clinical and prognostic importance of whole blood breast cancer early onset gene 1 (BRCA1) DNA methylation in sporadic breast cancer.

Methods: Genomic DNA was extracted from the peripheral blood cells (PBCs) of 902 breast cancer patients at diagnosis, with no BRCA1 mutation, and 990 control women. DNA methylation was measured by quantitative analysis of methylated alleles (QAMA) to estimate the extent of methylation of 2 CpG sites in the promoter region of BRCA1 oncosuppressor.

Results: BRCA1 promoter methylation rate in PBCs was 47.1% with a 95% confidence interval [46.1; 48.1] in breast cancer patients, and 45.9% with a 95% confidence interval [45.0; 46.8] in controls. We found a trend toward BRCA1 promoter hypermethylation in PBCs of sporadic breast cancer patients compared with controls. Association between methylation and clinicopathological features was evaluated using statistical tests. BRCA1 promoter methylation in PBCs increased significantly in breast cancer patients compared with controls, for age over 70 years (p=0.022), in post-menopausal status (p=0.013), for a body mass index (BMI) <20 (p=0.0095) or a waist-to-hip ratio (WHR) ≤76.8 (p=0.0027). We also found an association of increased BRCA1 promoter methylation in PBCs with ACA/ACA genotype for the SNP Thr594Thr in ESR (estrogen receptor gene), known to be associated with breast cancer risk (p=0.092), reflecting the reduced presence of this genotype in this breast cancer case-control study.

Conclusion: Analysis of site-specific DNA methylation in PBCs by QAMA provides quantitative DNA methylation values that may serve as important prognostic indicators.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • BRCA1 Protein / genetics*
  • Body Mass Index
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Case-Control Studies
  • DNA Methylation*
  • Epigenomics
  • Female
  • Genotype
  • Humans
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Postmenopause
  • Promoter Regions, Genetic
  • Receptors, Estrogen / genetics*
  • Risk Factors
  • Waist-Hip Ratio


  • BRCA1 Protein
  • BRCA1 protein, human
  • Receptors, Estrogen