Absence of the DNA repair enzyme human 8-oxoguanine glycosylase is associated with an aggressive breast cancer phenotype
Menée sur 96 patientes atteintes d'un cancer du sein de stade avancé et sur 20 patientes présentant des lésions non cancéreuses du sein, cette étude montre une association entre le niveau d'expression du gène d'une enzyme impliquée dans la réparation de l'ADN (8-oxoguanine glycosylase) et l'agressivité des tumeurs malignes
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.
British Journal of Cancer , résumé, 2010