10 years of mouse cancer modifier loci: human relevance

Abstract

About 10 years have elapsed since the first whole-genome scanning studies in the mouse to identify loci that affect susceptibility or resistance to tumorigenesis. In that time, >100 cancer modifiers have been mapped, and four strong candidate genes have been identified. Cancer modifier loci affect almost all types of mouse tumorigenesis, with some loci acting on the entire tumorigenic process, whereas others act on specific stages, e.g., tumor initiation or tumor growth/progression. Present evidence indicates that the effects of cancer modifier loci are tissue-specific and restricted to tumor cells. However, a subset of such loci may be involved in different types of tumors, and several chromosomal regions show significant clustering of cancer modifier loci. Human homologues of mouse cancer modifier loci most likely exist and play a role in the risk of sporadic cancer, although present experimental evidence for this possibility is sparse. Mouse cancer modifier loci might serve as the basis for understanding the genetic and biochemical mechanisms of polygenic inheritance of cancer predisposition/resistance. Identification of homologous cancer modifier loci in humans might, in turn, provide a step toward the development of diagnostic, preventive, and therapeutic strategies that target these loci.