Genetic factors in individual responses to environmental exposures.
Individual susceptibility to lung cancer due to occupational and environmental exposures to carcinogenic agents has been shown to be modulated by host-specific factors. The underlying principle of these factors is the differences that confer sensitivity or resistance to the disease. Since the majority of chemical carcinogens are not capable of causing hazardous effects per se, the metabolism of these compounds is a crucial part of the initial host response to the environmental exposure. Disturbances in the balance between activation and detoxification may thus explain the individual variations in responses to exposures to carcinogens. Many of the metabolic enzymes have recently been shown to express genetic polymorphisms in the population, and an association has been found between cigarette smoke-induced lung cancer and CYP1A1, CYP2D6, and GSTM1 genes. In addition, GSTM1 and NAT2 polymorphisms have been associated with susceptibility to bladder cancer. Since substantial ethnic differences exist in the distribution of altered and normal alleles, and findings in one ethnic group are not necessarily applicable to others, these biomarkers are still in the validation stage. However, as more information emerges on the specific features that lead to enhanced susceptibility they can undoubtedly be used to determine risks of environmental exposures to susceptible individuals and populations.
Hirvonen
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Institute of Occupational Health, Department of Industrial Hygiene and Toxicology, Helsinki, Finland.
D001191:Arylamine N-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D002273:Carcinogens / Q000633:toxicity*; D019363:Cytochrome P-450 CYP1A1; D019389:Cytochrome P-450 CYP2D6; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004198:Disease Susceptibility; D004781:Environmental Exposure / Q000009:adverse effects*; D015972:Gene Expression Regulation, Neoplastic; D005809:Genes, Regulator; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics*; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics*
D002273:Carcinogens; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1; D019389:Cytochrome P-450 CYP2D6; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; D005982:Glutathione Transferase