Impaired expression of glutathione peroxidase-4 gene in peripheral blood mononuclear cells: a biomarker of increased breast cancer risk.

Breast cancer aetiology is unclear despite comprising approximately 28% of female cancers. Several risk factors are known. Not all women exhibiting established risk factors will develop breast cancer but many without recognised risk factors will, indicating involvement of unknown risk factors. Impaired basal or oxidation-stimulated gene expression of redox enzymes, particularly Glutathione Peroxidase 1 and 4 (GPX1 and 4), resulting in increased oxidative stress, could be an "unknown" risk factor in breast cancer. We determined whether basal expression of GPX1 and 4, two major redox enzymes, in Peripheral Blood Mononuclear Cells (PBMNC) and/or their stimulated expression (oxidative stress) was impaired in women with breast cancer who have no known markers of risk compared with control women without breast cancer. A significant 30% impairment (p< 0.01) in basal PBMNC GPX4, but not GPX1, gene expression was observed in cancer patients. Oxidative stress stimulation in vitro did not increase GPX4 expression significantly in cancer patients or control women whereas GPX1 expression was significantly increased (30%, p<0.05) only in the cancer group. Attenuation of GPX4 mRNA expression in PBMNC suggests this could be a simple,early biomarker for future breast cancer risk in the high proportion of women without known risk factors who eventually contract the disease.