History of HNPCC
 
    Hereditary Non-Polyposis Colon Cancer was first described in 1913 by Aldred Scott Warthin (Ref. 1). Warthin's seamstress had told him that she would die at an early age from colon cancer or cancer of the female organs. When Warthin inquired about this prediction she said, "most of the members of my family die from these cancers." (Ref. 3) The woman died, as she predicted, of endometrial cancinoma, which prompted Warthin and his colleagues to begin a study of her family. Warthin published information about this family and a few others with multiple gastric and colorectal cancers spanning three generations. (Ref. 8) 
 
    The significance of Warthin's cancer prone families was not appreciated until 1966 when Henry Lynch began his research.. Lynch had discovered two other families and named the phenomenon Cancer Family Syndrome (CFS). (Ref. 1) Lynch continued his research and was the key investigator in much of the early characterization of the disease. CFS was eventually split into two different inheritable colon cancer diseases: Familial Adenomatous Polyposis (FAP) and Hereditary Non-polyposis Colon Cancer (HNPCC). More recently HNPCC has been sub-divided into Lynch syndrome I and Lynch syndrome II based on the location of cancer development.

    In 1993 the first of the HNPCC genes (MSH2) was discovered on chromosome 2 by Lauri Aaltonen and Paivi Peltomaki who were part of a multinational team researching the disease. (Ref. 9) Soon after, MLH1 was discovered on chromosome 3. It was determined that mutations in these two genes accounted for 90% of the known HNPCC families. (Ref. 7) Two other genes, PMS1 and PMS2 were later determined to also be involved in HNPCC.

Timeline for the discovery of the genes associated with inheritable colon cancer:

DePauw University HNPCC Home Page
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Created by:  April Bardes, Colin Connor, and Allison Niggemyer, Biology Department, DePauw University, Bios 354:  Molecular Genetics, Spring 1998.