DNA Repair Gene Expression Levels as Indicators of Breast Cancer in the Breast Cancer Family Registry

Anticancer Res. 2016 Aug;36(8):4039-44.

Abstract

Aim: The expression level of DNA repair-related genes and their association with breast cancer status among participants of the New York site of the Breast Cancer Family Registry was investigated.

Materials and methods: RNA from mononuclear cells in 194 sister sets (n=475 women) were assayed for ATM, BRCA1, MSH2, MUTYH and XPC gene expression levels and analyzed using generalized estimating equations (GEE).

Results: Individuals with decreased ATM and MSH2 expression had significantly higher odds for breast cancer compared to individuals with higher levels of expression (odds ratio (OR)=1.1, 95% confidence interval (CI)=1.02, 1.18) and (OR=1.90, 95% CI=1.21, 2.97), respectively. Upon stratifying the GEE model, reductions in ATM and MSH2 expression levels was heightened among women with an extended family history (FH) of breast cancer.

Conclusion: Reduced expression of ATM and MSH2 compromises DNA repair capacity and, thereby, increases breast cancer prevalence.

Keywords: Breast cancer; DNA repair; family history; gene expression.

MeSH terms

  • Adult
  • Aged
  • Ataxia Telangiectasia Mutated Proteins / biosynthesis*
  • Ataxia Telangiectasia Mutated Proteins / genetics
  • BRCA1 Protein / genetics
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Cycle Proteins / biosynthesis
  • Cell Cycle Proteins / genetics
  • DNA Glycosylases / genetics
  • DNA Repair / genetics
  • DNA-Binding Proteins / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genetic Predisposition to Disease*
  • Humans
  • Medical History Taking
  • Middle Aged
  • MutS Homolog 2 Protein / biosynthesis*
  • MutS Homolog 2 Protein / genetics
  • Mutation
  • Siblings

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • XPC protein, human
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • DNA Glycosylases
  • mutY adenine glycosylase
  • MSH2 protein, human
  • MutS Homolog 2 Protein