Enzymatic MPG DNA repair assays for two different oxidative DNA lesions reveal associations with increased lung cancer risk
Autor: | Edna Schechtman, Hedy S. Rennert, Mila Pinchev, Gad Rennert, Ziv Sevilya, Laurence S. Freedman, Yael Leitner-Dagan, Tamar Paz-Elizur, Dalia Elinger, Ran Kremer, Zvi Livneh |
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Rok vydání: | 2014 |
Předmět: |
Male
Oncology Cancer Research medicine.medical_specialty Pathology Lung Neoplasms DNA Repair DNA repair DNA damage Population Original Manuscript Adenocarcinoma Biology DNA Glycosylases Internal medicine medicine Humans education Lung cancer Lung Aged Neoplasm Staging education.field_of_study Case-control study Membrane Proteins Cancer General Medicine Odds ratio Prognosis medicine.disease Oxidative Stress DNA glycosylase Case-Control Studies Carcinoma Squamous Cell Leukocytes Mononuclear Female DNA Damage Follow-Up Studies |
Zdroj: | Carcinogenesis. 35:2763-2770 |
ISSN: | 1460-2180 0143-3334 |
Popis: | DNA repair is a major mechanism for minimizing mutations and reducing cancer risk. Here, we present the development of reproducible and specific enzymatic assays for methylpurine DNA glycosylase (MPG) repairing the oxidative lesions 1,N6-ethenoadenine (εA) and hypoxanthine (Hx) in peripheral blood mononuclear cells protein extracts. Association of these DNA repair activities with lung cancer was determined using conditional logistic regression with specimens from a population-based case-control study with 96 lung cancer cases and 96 matched control subjects. The mean MPG-εA in case patients was 15.8 units/μg protein (95% CI 15.3-16.3), significantly higher than in control subjects-15.1 (14.6-15.5), *P = 0.011. The adjusted odds ratio for lung cancer associated with a one SD increase in MPG-εA activity (2.48 units) was significantly bigger than 1 (OR = 1.6, 95% CI = 1.1-2.4; *P = 0.013). When activity of OGG1, a different DNA repair enzyme for oxidative damage, was included in the model, the estimated odds ratio/SD for a combined MPG-εA-OGG1 score was 2.6 (95% CI 1.6-4.2) *P = 0.0001, higher than the odds ratio for each single assay. The MPG enzyme activity assays described provide robust functional risk biomarkers, with increased MPG-εA activity being associated with increased lung cancer risk, similar to the behavior of MPG-Hx. This underscores the notion that imbalances in DNA repair, including high DNA repair, usually perceived as beneficial, can cause cancer risk. Such DNA repair risk biomarkers may be useful for risk assessment of lung cancer and perhaps other cancer types, and for early detection techniques such as low-dose CT. |
Databáze: | OpenAIRE |
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