DNA repair capacity as a possible biomarker of breast cancer risk in female BRCA1 mutation carriers

Br J Cancer. 2007 Jan 15;96(1):118-25. doi: 10.1038/sj.bjc.6603528.

Abstract

The BRCA1 gene product helps to maintain genomic integrity through its participation in the cellular response to DNA damage: specifically, the repair of double-stranded DNA breaks. An impaired cellular response to DNA damage is a plausible mechanism whereby BRCA1 mutation carriers are at increased risk of breast cancer. Hence, an individual's capacity to repair DNA may serve as a useful biomarker of breast cancer risk. The overall aim of the current study was to identify a biomarker of DNA repair capacity that could distinguish between BRCA1 mutation carriers and non-carriers. DNA repair capacity was assessed using three validated assays: the single-cell alkaline gel electrophoresis (comet) assay, the micronucleus test, and the enumeration of gamma-H2AX nuclear foci. DNA repair capacity of peripheral blood lymphocytes from 25 cancer-free female heterozygous BRCA1 mutation carriers and 25 non-carrier controls was assessed at baseline and following cell exposure to gamma-irradiation (2 Gy). We found no significant differences in the mean tail moment, in the number of micronuclei or in the number of gamma-H2AX nuclear foci between the carriers and non-carriers at baseline, and following gamma-irradiation. These data suggest that these assays are not likely to be useful in the identification of women at a high risk for breast cancer.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers, Tumor / chemistry
  • Biomarkers, Tumor / genetics*
  • Breast Neoplasms / genetics*
  • Comet Assay / methods
  • DNA / genetics*
  • DNA Repair*
  • Female
  • Gamma Rays
  • Genes, BRCA1*
  • Histones / chemistry
  • Histones / radiation effects
  • Humans
  • Immunohistochemistry
  • Lymphocytes / metabolism*
  • Lymphocytes / radiation effects
  • Micronucleus Tests
  • Middle Aged
  • Mutation
  • Predictive Value of Tests
  • Reference Values
  • Risk Factors
  • Sensitivity and Specificity
  • Software
  • Staining and Labeling
  • Statistics as Topic / methods
  • Surveys and Questionnaires

Substances

  • Biomarkers, Tumor
  • H2AX protein, human
  • Histones
  • DNA