Mismatch repair-proficient hereditary nonpolyposis colorectal cancer

Abstract

Approximately 40% of the families meeting the Amsterdam criteria for a diagnosis of hereditary nonpolyposis colorectal cancer lack evidence of heritable defects in the DNA mismatch repair (MMR) system; more specifically, these patients have no germline mutations in the MMR genes and, therefore, no tumor microsatellite instability or loss of immunohistochemical staining of MMR proteins. The proportion of nonpolyposis CRC families without MMR defects further increases when less stringent criteria for hereditary CRC are considered. As has been the case for other hereditary cancer syndromes, the identification of the genes associated with hereditary colorectal cancer would facilitate the molecular diagnosis of the disease and the development of appropriate surveillance guidelines and clinical management protocols for these patients. However, as will be discussed in this chapter, the identification of causal genes has not proven easy.