One of the greatest risk factors associated with carcinogenesis is age. Cancer risk increases exponentially toward the end of life in humans and other mammalian species [1]. Somatic genetic changes contribute significantly to the development of most tumors. However, the rate at which spontaneous mutations arise in normal adult cells has been hypothesized to be too low to generate all the genetic changes necessary to produce tumors at the observed rates [2]–[3]. Consequently, Loeb et al. developed the mutator hypothesis, which postulates an increased mutation rate in precancerous cells [3]. A variety of mechanisms could lead to such an increase, but a favored model is that sporadic mutations in, or epigenetic silencing of, genes responsible for maintaining genome integrity lead to increased rates of mutation. Once acquired, this mutator phenotype may serve as the driving force toward carcinogenesis as individuals age.
