DNA repair of oxidative DNA damage in human carcinogenesis: Potential application for cancer risk assessment and prevention

Efficient DNA repair mechanisms comprise a critical component in the protection against human cancer, as indicated by the high predisposition to cancer of individuals with germ-line mutations in DNA repair genes. This includes biallelic germ-line mutations in the MUTYH gene, encoding a DNA glycosyla...

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Published in:Cancer letters Vol. 266; no. 1; pp. 60 - 72
Main Authors: Paz-Elizur, Tamar, Sevilya, Ziv, Leitner-Dagan, Yael, Elinger, Dalia, Roisman, Laila C., Livneh, Zvi
Format: Journal Article
Language:English
Published: Ireland Elsevier Ireland Ltd 18.07.2008
Elsevier Limited
Subjects:
8-Oxoguanine
Animals
Comet Assay
DNA Damage
DNA Glycosylases - metabolism
DNA Repair
DNA repair enzymatic activity
Early detection
Early Diagnosis
Functional DNA repair assay
Guanine - analogs & derivatives
Hematology, Oncology and Palliative Medicine
Humans
Medical research
Mice
Mutation
Neoplasms - diagnosis
Neoplasms - enzymology
Neoplasms - genetics
OGG1
Oxidative stress
Risk Assessment
Smoking - adverse effects
DNA repair enzymatic activity
Oxidative stress
NSCLC
OGG1
PBMC
BER
Early detection
SNP
Functional DNA repair assay
HCR
ROS
8-Oxoguanine
NER
95% CI
non-small cell lung cancer
peripheral blood mononuclear cells
single nucleotide polymorphism
base excision repair
host-cell reactivation
95% confidence interval
reactive oxygen species
nucleotide excision repair
ISSN:0304-3835, 1872-7980
Online Access:Get full text
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Summary:Efficient DNA repair mechanisms comprise a critical component in the protection against human cancer, as indicated by the high predisposition to cancer of individuals with germ-line mutations in DNA repair genes. This includes biallelic germ-line mutations in the MUTYH gene, encoding a DNA glycosylase that is involved in the repair of oxidative DNA damage, which strongly predispose humans to a rare hereditary form of colorectal cancer. Extensive research efforts including biochemical, enzymological and genetic studies in model organisms established that the oxidative DNA lesion 8-oxoguanine is mutagenic, and that several DNA repair mechanisms operate to prevent its potentially mutagenic and carcinogenic outcome. Epidemiological studies on the association with sporadic cancers of single nucleotide polymorphisms in genes such as OGG1, involved in the repair of 8-oxoguanine yielded conflicting results, and suggest a minor effect at best. A new approach based on the functional analysis of DNA repair enzymatic activity showed that reduced activity of 8-oxoguanine DNA glycosylase (OGG) is a risk factor in lung and head and neck cancer. Moreover, the combination of smoking and low OGG activity was associated with a higher risk, suggesting a potential strategy for risk assessment and prevention of lung cancer, as well as other types of cancer.
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Incumbent of The Maxwell Ellis Professorial Chair in Biomedical Research. To whom all correspondence should be addressed: Dr. Zvi Livneh, Dept. of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel. Tel: 972-8-934-3203; Fax: 972-8-934-4169; Email: zvi.livneh@weizmann.ac.il
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2008.02.032