Epigenetics of breast cancer: Polycyclic aromatic hydrocarbons as risk factors

Brandon D. Jeffy, Ryan B. Chirnomas, Donato F. Romagnolo

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

In the absence of a causal relationship between the incidence of sporadic breast cancer and occurrence of mutations in breast cancer susceptibility genes, efforts directed to investigating the contribution of environmental xenobiotIcs in the etiology of sporadic mammary neoplasia are warranted. Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants, which have been shown to induce DNA damage and disrupt cell cycle progression. In this report we discuss published data pointing to PAHs as a risk factor in carcinogenesis, and present findings generated in our laboratory suggesting that the mammary tumorigenicity of PAHs may be attributable, at least in part, to disruption of BRCA-1 expression by reactive PAH-metabolites. We report that benzo[a]pyrene (B[a]P), selected as a prototype PAH, disrupts BRCA-1 transcription in estrogen receptor (ER)-positive but not ER-negative breast cancer cells. The reduced potential for BRCA-1 expression in B[a]P-treated cells coincides with disruption of cell cycle kinetics and accumulation of p53. These effects are counteracted by the AhR-antagonist α-naphthoflavone (ANF), and in breast cancer cells expressing mutant p53 or the E6 human papilloma virus protein. We suggest that exposure to PAHs may be a predisposing factor in the etiology of sporadic breast cancer by disrupting the expression of BRCA-1.

Original languageEnglish (US)
Pages (from-to)235-244
Number of pages10
JournalEnvironmental and Molecular Mutagenesis
Volume39
Issue number2-3
DOIs
StatePublished - Apr 9 2002

Keywords

  • Aromatic hydrocarbon receptor
  • BRCA-1
  • Estrogen receptor
  • Polycyclic aromatic hydrocarbons
  • p53

ASJC Scopus subject areas

  • Epidemiology
  • Genetics(clinical)
  • Health, Toxicology and Mutagenesis

Fingerprint Dive into the research topics of 'Epigenetics of breast cancer: Polycyclic aromatic hydrocarbons as risk factors'. Together they form a unique fingerprint.

  • Cite this