Modifiers of expression in mutations of mismatch repair gene carriers in hereditary nonpolyposis colorectal cancer

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disorder caused by germline mutations in DNA mismatch repair (MMR) genes. Patients with this syndrome are at increased risk for a variety of cancers. Among individuals with MMR mutations, there is considerable variation in the age of cancer onset, probably resulting from a combination of other genetic and environmental factors. This review describes recent advances in identifying these genetic risk factors in HNPCC patients with MMR mutations. Recent research has identified potential modifiers of MMR gene expression that are involved in cell cycle control, DNA repair, and metabolism and the pathways through which these modifiers act. These findings will be important in identifying individuals that are more susceptible to developing cancer at an earlier age and may aid in the development of strategies to prevent HNPCC.