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Semin Cancer Biol. 2000 Jun;10(3):201-10.

Impacts of chemicals on liver cancer risk.

Author information

1
Division of Bioengineering and Environmental Health, Massachusetts Institute of Technology, Cambridge 02139, USA.

Abstract

Primary liver cancer (PLC) is of multifactorial etiology. Chronic infections by hepatitis B (HBV) and hepatitis C (HCV) viruses are major risk factors for most PLC cases worldwide, although mechanisms through which the infections cause PLC are still unknown. Epidemiologic and experimental evidence indicates that exposure to certain chemicals can also contribute significantly to PLC development, some of which have been designated as human liver carcinogens (Group 1) by the International Agency for Research on Cancer. These include aflatoxins and chronic consumption of alcoholic beverages. Many naturally occurring and synthetic chemicals have been shown to induce liver cancer in experimental animals. Humans are exposed to these carcinogens via accidental contamination of food or water; usually at levels far lower than those that are carcinogenic to experimental animals. Consequently, assessment of possible human PLC risk associated with such exposures is complex and uncertain. Evidence regarding aflatoxin as a human carcinogen has been extensively documented and is reviewed as an example of the usefulness of parallel experimental and epidemiological investigations in cancer risk assessment. Aflatoxins are toxic metabolites of certain spoilage molds that are potent liver carcinogens in experimental animals and frequently contaminate human diets. Collectively, epidemiologic data together with evidence from many types of experimental models defines the role of aflatoxin exposure in PLC causation. Molecular epidemiology involving the use of biomarkers of exposure has been particularly effective in linking aflatoxin exposure to PLC. Biomarkers of aflatoxin exposure have been validated with particular thoroughness. Dose-response relationships between biomarker levels and liver tumor incidence were first established in experimental animals. The biomarkers were then employed in pilot studies of limited scale in humans to define sensitivity, specificity, accuracy, and reliability parameters. Further validation in transitional epidemiological studies assessed intra- and interindividual variability, background levels, external dose-marker relationship, and feasibility for use in larger population-based studies. Finally, prospective epidemiological studies were conducted to evaluate biomarker effectiveness in identifying PLC risk.

PMID:
10936069
DOI:
10.1006/scbi.2000.0320
[Indexed for MEDLINE]

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