Cancer is the result of multiple genetic and epigenetic changes (Vogelstein and Kinzler, 2004) which result in a set of phenotypes referred to as the “hallmarks of cancer” (Hanahan and Weinberg, 2000). Evidence from the number of mutations in cancer genomes also supports the concept that a mutator phenotype is an important early step in the carcinogenic process (Loeb, 2011). Early acquisition of a mutator phenotype increases the cellular mutation rate, thereby facilitating additional mutations necessary to produce an invasive cancer. However, in the epidemiologic literature, these fundamental aspects of cancer biology are generally not addressed. Furthermore, there is a lack of consideration of the length of time necessary for human cancer to develop, and the implications of this time course on the interpretation of epidemiologic studies.
