Reduced Repair of the Oxidative 8-Oxoguanine DNA Damage and Risk of Head and Neck Cancer

Abstract

An increasing number of studies indicate that reduced DNArepair capacity is associated with increased cancer risk. Using a functional assay for the removal of the oxidative DNA lesion 8-oxoguanine by the DNA-repair enzyme 8-oxoguanine DNA glycosylase 1 (OGG1), we have previously shown that reduced OGG activity is a risk factor in lung cancer. Here, we report that OGG activity in peripheral blood mononuclear cells from 37 cases with squamous cell carcinoma of the head and neck (SCCHN) was significantly lower than in 93 control subjects, frequency matched for age and gender. Retesting of OGG activity 3 to 4 years after diagnosis and successful treatment of 18 individuals who recovered from the disease showed that OGG activity values were similar to those determined at diagnosis, suggesting that reduced OGG activity in case patients was not caused by the disease. Logistic regression analysis indicated that the adjusted odds ratio (OR) associated with a unit decrease in OGG activity was statistically significantly increased [OR, 2.3; 95% confidence interval (95% CI), 1.5-3.4]. Individuals in the lowest tertile of OGG activity exhibited an increased risk of SCCHN with an OR of 7.0 (95% CI, 2.0-24.5). The combination of smoking and low OGG was associated with a highly increased estimated relative risk for SCCHN. These results suggest that low OGG is associated with the risk of SCCHN, and if confirmed by additional epidemiologic studies, screening of smokers for low OGG activity might be used as a strategy for the prevention of lung cancer and SCCHN. (Cancer Res 2006; 66(24): 11683-9)

Low Integrated DNA Repair Score and Lung Cancer Risk

“…This approach assumes that (i) DNA repair activity in PBMC is a legitimate surrogate for DNA repair in other tissues, and (ii) each individual has a personal baseline capacity to repair DNA. These assumptions are supported by previous results showing that the activity of the DNA repair enzyme OGG1 in PBMC correlates to the activity in lung tissue (13), and that individuals exhibit a personal OGG1 activity that is stable over several years (13) and does not significantly change years after recovery from cancer (15). Using this approach we found that low OGG1 enzymatic activity is associated with the risk of lung cancer (13) and head and neck cancer (15).…”

“…These assumptions are supported by previous results showing that the activity of the DNA repair enzyme OGG1 in PBMC correlates to the activity in lung tissue (13), and that individuals exhibit a personal OGG1 activity that is stable over several years (13) and does not significantly change years after recovery from cancer (15). Using this approach we found that low OGG1 enzymatic activity is associated with the risk of lung cancer (13) and head and neck cancer (15). In addition, we found that increased enzymatic activity of MPG, a DNA repair enzyme of the DNA glycosylases family, which removes from DNA multiple alkylation and oxidative lesions, is associated with increased lung cancer risk (18).…”

“…To measure such interindividual variations in DNA repair, we (13)(14)(15)(16)(17)(18) and others (19)(20)(21) took the approach of measuring the enzymatic activity of specific DNA repair enzymes, using peripheral blood mononuclear cell (PBMC) as the reporter tissue. Our primary focus was on DNA repair enzymes that target oxidative DNA damage, which has been implicated as a major factor in carcinogenesis (22).…”

Salivary analysis of oral cancer biomarkers

“…Similarly, it was recently reported that in malignant tissues (in transitional meningioma and in glioblastoma multiforme) the degree of oxidative DNA damage (8OHdG) is increased whereas the total anti-oxidant capacity is decreased Tuzgen et al, 2007) Indeed, efficient DNA repair mechanisms comprise a critical component in the protection against cancer and among these the 8-oxoguanine DNA glycosylase (OGG1) enzyme is crucial for repairing the oxidative DNA lesion 8OHdG that is highly mutagenic and carcinogenic. Most importantly is that reduced activity of OGG1 is considered an established risk factor for various cancers such as lung and head and neck cancer (Paz-Elizur et al, 2006. Hence, the reduction observed in salivary OGG1 in the OSCC patients is expected.…”

Cigarette smoke-induced DNA damage and repair detected by the comet assay in HPV-transformed cervical cells

“…8-Oxoguanine is a common mutagenic DNA lesion which is formed abundantly by intracellular oxidation and exogenous carcinogens like cigarette smoke (15,16). It has also been shown that cigarette smoke induces other forms of DNA damage, including single-strand breaks (SSBs) (17,18) and possibly double-strand breaks (DSBs) (19,20).…”