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The background mutation rate occurs from infidelities in DNA replication or from toxic metabolites, such as reactive oxygen species. In addition, exogenous carcinogens, such as ultraviolet radiation, accelerate mutagenesis. When mutations land in critical growth-related genes, cancer often forms. However, not all cells with oncogenic mutations become cancerous. For instance, in familial cancer syndromes, every cell in the body inherits the defect, but only a limited number of cancers develop. What modulates the risk for cancer formation in the face of oncogenic mutation? One hypothesis proposes “modifier” genes that increase or decrease the likelihood of developing cancer in response to oncogenic change. These modifiers are tremendously imp…