Interaction between Dose and Susceptibility to Environmental Cancer: A Short Review
Eino Hietanen,1 Kirsti Husgafvel-Pursiainen,2 and
Harri Vainio2
1Department of Clinical Physiology, University of Turku, Turku, Finland
2Institute of Occupational Health, Topeliuksenk, Helsinki, Finland
Abstract
Increased risk of environmentally induced cancer is associated with various types of exposures and host factors, including differences in carcinogen metabolism. Since many carcinogenic compounds require metabolic activation to enable them to react with cellular macromolecules, individual features of carcinogen metabolism may play an essential role in the development of environmental cancer. In this context, cigarette smoking has often been the main type of carcinogenic exposure examined in human studies. Increasing attention has recently been paid to the dose level at which individual susceptibility may be observed. Present studies on increased risk of smoking-related lung cancer associated with phenotypic or genotypic variation of the genes encoding for CYP1A1 or CYP2D6 enzymes are summarized. Similarly, higher risks of lung or bladder cancer seen at various levels of smoking in association with polymorphism of the glutathione S-transferase gene GSTM1 or NAT1 and NAT2 genes involved in N-acetylation are reviewed. Finally, the influence of CYP2E1, GSTM1, or the combined at-risk genotype on the risk of hepatocellular carcinoma in smokers is briefly discussed. -- Environ Health Perspect 105(Suppl 4):749-754 (1997)
Key words: cancer, cytochrome, exposure, genotype, glutathione, susceptibility
This paper was prepared as background for the Workshop on Susceptibility to Environmental Hazards convened by the Scientific Group on Methodologies for the Safety Evaluation of Chemicals (SGOMSEC) held 17-22 March 1996 in Espoo, Finland. Manuscript received at EHP 5 November 1996; accepted 18 November 1996.
The authors acknowledge financial support obtained from the Academy of Finland, project 29456.
Address correspondence to Dr. E. Hietanen, Department of Clinical Physiology, Turku University Hospital, FIN-20520 Turku, Finland. Telephone (358) 21-2612664. Fax (358) 21-2611666. E-mail: einohietanen@utu.fi
Abbreviations used: CI, confidence interval; CYP, cytochrome P450-related enzymes; EM, extensive metabolizer; GST, glutathione S-transferase; NAT, N-acetyltransferase; OR, odds ratio; PM, poor metabolizer.
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