Biological Markers for Exposures Epidemiology 243 Molecular Epidemiology of Cancer
Early Studies • MacMahon: Geographical correlation of urinary estrogen concentrations with cancer of the breast (1974) • Cole & MacMahon: Urinary and blood estrogens and breast cancer in case-control studies (1969,1982, 1983) • McMichael: The relationship between cancer mortality and serum cholesterol concentrations (1984)
Recent Studies • Aflatoxins and hepatitis B on liver cancer in a cohort study, including measurements of urinary metabolites and nucleic acid adducts of aflatoxin (Ross, 1992, 1994) • The relationship between HPV and cervical cancer (Munoz, 1992, Bosch, 1995)
Application of biomarkers in Epidemiology Molecular markers can be applied to increase the accuracy of measurements • of genetic and other acquired susceptibility to disease; • of exposures that may cause or prevent disease; • of exposures that confound or modify the associations between risk and other exposures • of disease itself • of factors that may determine the outcome of the disease such as precursors and stages
Application of biomarkers in Epidemiology Biomarkers may also be used • to reduce the time interval between the relevant exposure and measurement of the putative effect • To increase the yield of information on disease pathogenesis • To increase the cost-effectiveness of epidemiological studies. More information is gained per unit cost.
Biomarker in Epidemiology: Biomarkers of Biological Agents • Biological agents associated with chronic infection and subsequent development of cancer are measured using serological or nucleic acid markers.
Biomarker in Epidemiology: Biomarkers of Biological Agents • HPV DNA by PCR-based assays HPV infection is often transient, especially in young women so that repeated sampling is required to assess persistent HPV infections
HPV Testing and Typing • HPV infection is the main cause of cervical cancer. Transient in women. Only 10-20% persistent infections are at risk of neoplasia • About 70 subtypes, of which 25 are tropic for genital tract. Those are subdivided into three categories:
HPV Testing and Typing • HPV can be tested and typed by dot blot hybridization, southern blot hybridization, Hybrid Capture and PCR • High sensitivity but relatively low specificity, particular among young women • HPV typing has great potential as a primary screening tool for cervical cancer.
Biomarker in Epidemiology: Biomarkers of Biological Agents HBV infection by serological assays. • There are serological markers that distinguish between past and persistent infections. HBV DNA detection in sera further refines the assessment of exposure.
Major Risk Factors for Stomach Cancer in Chinese Population • Helicobacter pylori was the first bacterium to be officially recognized as a cancer-causing agent.
Major Risk Factors for Stomach Cancer in Chinese Population • Helicobacter pylori Infection. Nitrates and nitrites are substances commonly found in cured meats, some drinking water, and certain vegetables, that can be converted by Helicobacter pylori, into compounds that have been found to cause stomach cancer in animals.