Absence of the DNA repair enzyme human 8-oxoguanine glycosylase is associated with an aggressive breast cancer phenotype

Br J Cancer. 2012 Jan 17;106(2):344-7. doi: 10.1038/bjc.2011.518. Epub 2011 Nov 22.

Abstract

Background: 8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is the most abundant marker of DNA damage and it reflects oxidative stress. Human 8-oxoguanine glycosylase (hOGG1) is a DNA-repair enzyme that participates in 8-oxodG removal.

Methods: hOGG1 protein expression was immunohistochemically studied in 96 patients with local or locally advanced breast cancer and in 20 lesions of non-malignant breast disease. 8-OxodG levels had been previously determined in all patients.

Results: hOGG1 was overexpressed in invasive vs non-invasive lesions (P=0.006). 8-OxodG and hOGG1 had a significant inverse association (P=0.046). Lack of hOGG1 expression was associated with the most poor prognostic factors of breast cancer. In addition, all triple-negative breast carcinomas (TNBCs) were hOGG1 negative (P=0.027 vs non-TNBCs). Patients with a lack of both hOGG1- and 8-oxodG immunostaining showed extremely poor breast cancer-specific survival compared with those with either 8-oxodG- or hOGG1-positive tumours (P<0.000005).

Conclusion: The current results imply that absence of hOGG1 expression is associated with features of aggressive breast cancer. Tumours lacking both 8-oxodG and hOGG1 seem to indicate especially poor prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / enzymology
  • Breast Neoplasms / pathology*
  • DNA Glycosylases / metabolism*
  • DNA Repair*
  • Female
  • Humans
  • Immunohistochemistry
  • Phenotype

Substances

  • DNA Glycosylases
  • oxoguanine glycosylase 1, human