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Pharmacogenetics: detecting sensitive populations

¹Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892, USA.

Environmental Health Perspectives

|December 1, 1994

Summary

Current cancer risk models overlook genetic predispositions. Incorporating genetic polymorphisms in cytochrome P450 enzymes and measuring carcinogen-DNA adducts can improve cancer risk assessment by identifying sensitive populations.

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Area of Science:

Toxicology
Genetics
Cancer Research

Background:

Risk assessment models aim to predict human health risks from toxic agents, incorporating safety factors.
Cancer development is a multistage process influenced by carcinogen exposure, genetic factors, and endogenous processes.
Existing models often neglect genetic predispositions affecting individual sensitivity to carcinogens.

Purpose of the Study:

To highlight the limitations of current risk assessment models in cancer.
To emphasize the role of genetic polymorphisms in cytochrome P450 enzymes in cancer risk.
To propose the integration of genetic and biomarker data for enhanced risk assessment.

Main Methods:

Review of scientific literature on cancer risk assessment, genetic polymorphisms, and cytochrome P450 enzymes.
Discussion of carcinogen-DNA adducts as biomarkers of exposure and metabolic processing.
Exploration of the combined use of genotyping and adduct assays for risk evaluation.

Main Results:

Genetic polymorphisms in cytochrome P450 enzymes (e.g., CYP1A1, CYP2E1, CYP2D6) are linked to varying cancer risks, particularly lung cancer.
The frequencies of these genetic variations differ across ethnic and racial groups.
Carcinogen-DNA adduct levels reflect the integrated effects of exposure and an individual's metabolic capacity, which is genetically influenced.

Conclusions:

Current cancer risk assessment models are insufficient due to their failure to account for genetic variability.
Genotyping for polymorphic cytochrome P450 enzymes can identify susceptible individuals.
Combining genetic data with carcinogen-DNA adduct measurements offers a more comprehensive approach to cancer risk assessment.

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