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Genetic variability in susceptibility and response to toxicants
M C Miller1, H W Mohrenweiser, D A Bell
1National Institute of Environmental Health Sciences, 111 Alexander Drive, Building 101, Room B323, P.O. Box 12233, C3-03, Research Triangle Park, NC 27709, USA.
Toxicology Letters
|April 27, 2001
Summary
Genetic variations in detoxification and DNA repair genes influence individual susceptibility to environmental toxins and carcinogens, impacting disease risk, particularly bladder cancer in smokers.
Area of Science:
- Environmental Health
- Genetics
- Cancer Research
Background:
- Individual susceptibility to environmental exposures varies due to polymorphic traits.
- Metabolism of toxins is influenced by inherited variations in genes like CYP, NAT, and GST.
- DNA repair gene variations can affect somatic mutation rates and cancer risk.
Purpose of the Study:
- To investigate the association between genetic variations in environmental response genes and disease risk.
- To determine if genetic variations impact gene function and susceptibility to environmentally caused diseases.
Main Methods:
- Genotyping for specific gene variants (GSTM1, NAT1/2, XRCC1, XPD).
- Assessing the relationship between genotypes and disease risk (e.g., bladder cancer in smokers).
- Evaluating the functional impact of genetic variation on gene expression and repair mechanisms.
Main Results:
- Specific 'at risk' genotypes for GSTM1 and NAT1/2 were found to increase bladder cancer risk in smokers.
- Variants in DNA repair genes (XRCC1, XPD) appear to modify damage from environmental exposures like cigarette smoke and radiation.
Conclusions:
- Inherited genetic variations in detoxification and DNA repair pathways contribute to susceptibility to environmentally induced diseases.
- Understanding these genetic factors is crucial for evaluating individual risk for diseases caused by environmental exposures.
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