ABSTRACT
Two fundamental principles that underlie current studies of molecular epidemi ology relate to the complexity of the carcinogenesis process and the fact that individuals vary in response to carcinogenic exposures. For the first, cancer is a multistage process where each stage is caused by several genetic mutations. These mutations are the result of several steps, beginning with an exogenous exposure (e.g. chemicals, radiation, or viruses), endogenous exposure (e.g. oxy-radicals), or enzymatic error (e.g. polymerase or recombinase infidelity). But, following these exposures, several processes must occur or go awry. For example, chemical expo sures by themselves are not sufficient to cause cancer. Before the mutation occurs, a potential chemical carcinogen has to be absorbed, undergo metabolic activation (which frequently requires several enzymatic steps), escape detoxification, be trans ported to a target organ, adduct a critical protooncogene or tumor suppressor gene, escape DNA repair, and escape other mechanisms to control the damage, such as cell death. Thus, the multistage process of carcinogenesis is a very complicated process consisting of multiple steps and pathways. This complexity leads to diffi culties in the design and interpretation of studies, and the need to formulate a priori hypotheses is critical.
