EVIDENCE FROM CANCER INTERVENTION AND BIOMARKER STUDIES AND THE DEVELOPMENT OF BIOCHEMICAL MARKERS

Evidence from intervention trials with vitamins E and C and beta-carot ene are reviewed as well as evidence from trials that have used interm ediate endpoints with a special emphasis on biomarkers of cancer of th e colorectum. The methodologic issues that require resolution before a second generation of clinical trials are launched to assess the effic acy of these antioxidants in the prevention of cancer are identified. Specific concerns regarding the validation of pathologic biomarkers of cancer and biochemical markers of mechanism of action for the antioxi dants are discussed. Cellular proliferation indexes in the colon are u sed as an example of pathologic biomarkers for cancer and the measurem ent of plasma and tissue malondialdehyde concentrations is used as an example of problems with the development of biochemical markers of oxi dative stress that can be used in prevention trials. The use of DNA ox idation products as promising biomarkers is also discussed.