Figure 21-1 Biomarkers in cancer etiology Biomarkers in cancer etiologic studies can be classified into three broad categories: biomarkers of exposure, biomarkers of effect, and biomarkers of susceptibility. Biomarkers of susceptibility (cancer risk) can be derived from each of the steps along the continuum of the carcinogenic process, reflecting interindividual variations in absorption, distribution, metabolism (activating and detoxifying), and excretion of carcinogens; sensitivity to formation of macromolecule (DNA and protein) adducts; and ability to repair macromolecule damage, restore normal cellular functions, and eliminate premalignant cells.
Biomarkers of Internal Dose
Biomarkers of internal dose measure levels of a carcinogen or its metabolite in human tissues, bodily fluids, and excreta. 5 These biomarkers are not bound to cellular targets but provide a measure of exposure, absorption, metabolism, and excretion. There is generally a good correlation between external exposure and internal dose; however, the involvement of absorption and metabolism and interindividual variation in these processes suggest that the relationship may not always be simple. One of the classical examples of validated biomarkers of internal dose that contributed greatly to elucidate the environmental cause of human cancer is urinary aflatoxin and its metabolites. Aflatoxins have long been suspected to be human hepatic carcinogens, but the strongest evidence came from a prospective nested case-control study in which the authors measured urinary aflatoxin B1 (AFB1), its metabolites AFP1 and AFM1, and DNA adducts (AFB1-N7-Guanine) to assess the relation between aflatoxin exposure and liver cancer. Subjects with liver cancer were more likely to have detectable concentrations of any of the aflatoxin metabolites than controls, and the highest relative risk was for AFP1 (6.2-fold). Moreover, there was a strong interaction between chronic hepatitis B infection and aflatoxin exposure in liver cancer risk. 6
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