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Risk assessment: the importance of genetic polymorphisms in man
L E Knudsen1, S H Loft, H Autrup
1Department of Environmental and Occupational Medicine, Institute of Public Health, University of Copenhagen, Blegdamsvej 3 DK-2200 Copenhagen N, Denmark. lisbeth.knudsen@pubhealth.ku.dk
Mutation Research
|September 6, 2001
Summary
Genetic polymorphisms in metabolism enzymes significantly impact cancer risk, especially when combined with environmental exposures like air pollution. Certain genotypes, like GSTM1 null and NAT2 slow, increase susceptibility, potentially raising cancer risk beyond accepted safety factors.
Area of Science:
- Environmental Health
- Genetic Epidemiology
- Toxicology
Background:
- Genetic polymorphisms in metabolic enzymes are linked to cancer risk, with varying relative risk estimates across studies.
- Some polymorphisms act as effect modifiers, influencing disease risk only in the presence of specific exposures.
- Individual susceptibility to environmental toxicants can be significantly altered by genetic makeup.
Purpose of the Study:
- To investigate the role of genetic polymorphisms in the metabolism of environmental toxicants.
- To assess the impact of traffic-generated air pollution on chromosomal aberrations in relation to specific genotypes.
- To evaluate the concept of effect modification in cancer risk assessment.
Main Methods:
- Case-control and cohort study designs were reviewed.
- Analysis of chromosomal aberrations in relation to specific genetic polymorphisms (GSTM1 null, NAT2 slow) and exposure to traffic air pollution.
- Literature review on genetic polymorphisms and cancer risk assessment safety factors.
Main Results:
- Statistically significant higher levels of chromosomal aberrations were observed in non-smoking bus drivers with GSTM1 null and NAT2 slow genotypes exposed to traffic air pollution.
- These findings suggest effect modification of cancer risk by genetic polymorphisms.
- The cumulative effect of multiple susceptibility genotypes and other factors (e.g., DNA repair, nutrition) may elevate cancer risk substantially.
Conclusions:
- Genetic polymorphisms in metabolic enzymes play a crucial role in modifying cancer risk associated with environmental exposures.
- The study highlights the importance of considering combined genetic susceptibility and environmental factors in risk assessment.
- Current safety factors in risk assessment may underestimate the risk for individuals with multiple susceptibility determinants.