title: History, genetics, and strategies for cancer prevention in Lynch syndrome.
abstract: Colorectal cancer (CRC) is the most common gastrointestinal malignancy and the third cause of cancer death in men and women in the United States. The majority of CRC cases diagnosed annually are due to sporadic events, but up to 6% are attributed to known monogenic disorders that confer a markedly increased risk for the development of CRC and multiple extracolonic malignancies. Lynch syndrome is the most common inherited CRC syndrome and is associated with mutations in DNA mismatch repair genes, mainly MLH1 and MSH2 but also MSH6, PMS2, and EPCAM. Although the risk of CRC and endometrial cancer may approach near 75% and 50%, respectively, in gene mutation carriers, the identification of these individuals and at-risk family members through predictive genetic testing provides opportunities for cancer prevention including specialized cancer screening, intensified surveillance, and/or prophylactic surgeries. This article will provide a review of the major advances in risk assessment, molecular genetics, DNA mutational analyses, and cancer prevention and management made since Lynch syndrome was first described 100 years ago.
authors.affiliation: Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York; Division of Digestive and Liver Diseases, Columbia University Medical Center, New York, New York. Electronic address: fk18@columbia.edu.
authors.forename: Fay
authors.initials: F
authors.lastname: Kastrinos
authors.affiliation: University of Michigan Health System, Ann Arbor, Michigan.
authors.forename: Elena M
authors.initials: EM
authors.lastname: Stoffel
mesh_terms: D000328:Adult; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis* / Q000235:genetics / Q000266:history / Q000517:prevention & control*; D005260:Female; D005762:Gastroenterology / Q000379:methods / Q000639:trends*; D005820:Genetic Testing / Q000379:methods; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D008297:Male; D008875:Middle Aged; D013514:Surgical Procedures, Operative / Q000379:methods; D014481:United States / Q000453:epidemiology
keywords: Colorectal Cancer; Lynch Syndrome
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