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Variability in nucleotide excision repair and cancer risk: a review
1Unit of Cancer Epidemiology, INSERM U521, Institut Gustave Roussy, 39 rue Camille Desmoulins, Villejuif, France.
Abstract:
Cancer initiation is classically associated with the induction of mutations on specific oncogenes or tumor suppressor genes, due to the presence of unrepaired DNA lesions produced by endogenous or exogenous genotoxic agents. Among several DNA repair pathways, the nucleotide excision repair (NER) is the most important and versatile one in removing the bulky adducts induced by physical and chemical carcinogens. Xeroderma pigmentosum (XP), characterized by a deficiency in NER and an over 1000-fold increased risk of skin cancer, represents a paradigm to understand the role of unrepaired lesion in the development of cancer. We reviewed here several NER assays used in epidemiological studies investigating the association between DNA repair efficiency and cancer risk. Reduced DNA repair could contribute to the development of cutaneous basal cell carcinoma (BCC), although discordant results have been reported. More consistent findings were observed between cellular sensitivity towards genotoxic agents and smoking-related cancers.
Insights
This review highlights nucleotide excision repair (NER) assays for studying cancer risk. Reduced DNA repair efficiency is linked to skin cancers and smoking-related cancers.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- Cancer initiation involves mutations from unrepaired DNA lesions caused by genotoxins.
- Nucleotide excision repair (NER) is crucial for removing bulky DNA adducts from carcinogens.
- Xeroderma pigmentosum (XP) demonstrates the link between NER deficiency and high skin cancer risk.
Purpose of the Study:
- To review NER assays used in epidemiological studies.
- To investigate the association between DNA repair efficiency and cancer risk.
Main Methods:
- Literature review of epidemiological studies utilizing NER assays.
- Analysis of associations between DNA repair capacity and various cancer types.
Main Results:
- Reduced DNA repair efficiency may contribute to basal cell carcinoma (BCC) development, though findings are inconsistent.
- Consistent associations were found between cellular sensitivity to genotoxins and smoking-related cancers.
Conclusions:
- NER assays are valuable tools for cancer risk assessment.
- DNA repair efficiency, particularly NER, plays a significant role in cancer development, especially for skin and smoking-related cancers.