8-Hydroxydeoxyguanosine: a new potential independent prognostic factor in breast cancer

Abstract

BACKGROUND: is the commonly used marker of oxidative stress-derived DNA damage. 8-OxodG formation is regulated by local antioxidant capacity and DNA repair enzyme activity. Earlier studies have reported contradictory data on the function of 8-oxodG as a prognostic factor in different cancer types. METHODS: We assessed pre-operative serum 8-oxodG levels with an enzyme-linked immunosorbent assay in a well-defined series of 173 breast cancer patients. 8-OxodG expression in the nuclei of cancer cells from 150 of these patients was examined by immunohistochemistry. RESULTS: The serum 8-oxodG levels and immunohistochemical 8-oxodG expression were in concordance with each other (Po0.05). Negative 8-oxodG immunostaining was an independent prognostic factor for poor breast cancer-specific survival according to the multivariate analysis (Po0.01). This observation was even more remarkable when ductal carcinomas only (n ¼ 140) were considered (Po0.001). A low serum 8-oxodG level was associated statistically significantly with lymphatic vessel invasion and a positive lymph node status. CONCLUSIONS: Low serum 8-oxodG levels and a low immunohistochemical 8-oxodG expression were associated with an aggressive breast cancer phenotype. In addition, negative 8-oxodG immunostaining was a powerful prognostic factor for breast cancer-specific death in breast carcinoma patients.

The Role of Biomarkers of Oxidative Stress in Breast Cancer Risk and Prognosis: A Systematic Review of the Epidemiologic Literature

“…48 In 2010, Sova et al reported that negative 8-oxodG tumor status based on immunohistochemistry was associated with lower breast cancer-specific survival (BCSS). 49 This study also reported that serum 8-oxodG, from blood collected before surgery, was not associated with BCSS, but data were not shown. Two small Finnish cohort studies evaluated 8-oxodG tumor status in association with BCSS, with the first evaluating 8-oxodG alone 50 and the second evaluating 8-oxodG in combination with 8-oxoguanine glycosylase.…”

Effect of dihydropyrrol and maleimide derivatives on the state of the liver and colon in normal rats and those with colorectal carcinogenesis induced by dimethylhydrazine

“…Вільнорадикальне окислення зумовлює пошкодження біомакромолекул, зокрема нуклеїнових кис-лот, основними продуктами окислення яких є 8-гідроксидезоксигуанозин (окислений 2′-гуанін, 8-oxoG), формамідопіримідини, 5-гідроксиурацил [21], що може призво-дити до загибелі клітин шляхом апопто-зу чи некрозу або до злоякісного переро-дження [22,23]. Зростання рівня 8-oxoG у біологічних рідинах і, передусім, у сечі ча-сто є показником наявності та прогресуван-ня згаданих патологічних процесів [18,20,24]. Визначення цього біохімічного маркера дозволяє оцінити перебіг пухлинного про-цесу та ефективність протипухлинної терапії [23], а також генотоксичність протипухлин-…”

Role of DNA polymerase β oxidized nucleotide insertion in DNA ligation failure

“…There are many reports describing elevated and altered levels of oxidation products of purine or pyrimidine bases in a plethora of ageing-related diseases, such as cancer [7, 10]. For example, an increase in the ratio of 8-oxodG monophosphate (8-oxodGMP) to 8-oxodGTP in the nucleotide pool has been reported in cancer cells, such as in breast carcinoma [11, 12]. The deleterious effects of oxidized dNTPs stem from their incorporation into DNA during DNA replication and repair [13].…”