Abstract
The paper examines the adenoma to carcinoma sequence proposed by B. Volgenstein and E.R. Fearon. The paper explains how this model acts as a basis for understanding the mechanisms which are thought to cause eighty per cent of sporadic colon cancers and cases of familial adenematous polyposis. The paper also describes an alternative pathway resulting in microsatellite instability and thought to underlie cases of hereditary non polyposis colon cancer. In addition, the paper looks at the molecular events involving mutated mismatch repair enzymes.

From the Paper
"Colorectal cancer causes approximately 15,000 deaths per year in the U.K and about 30,000 individuals are diagnosed with it each year making it the second most common cause of death from cancer. Of these, about 70% are colon cancers which affect men and women and are much more prevalent in the Western World than India or Asia. About 25% of colon cancers occur where there's a family history of it but only 5% are due to known familial syndromes. These include Familial adenomatous polyposis (FAP); a mendelian dominant disorder which sees a germline mutation of APC and hereditary non polyposis colon cancer (HNPCC); a disorder in which germline mutations in mismatch repair enzymes are caused. The other 20% of clusters of colon cancer in families are unexplained but postulated risks are "mild" APC and mismatch repair gene mutations or polymorphisms of genes involved in nutrient or carcinogen metabolism and also non genetic factors. The main proportion of colon cancer though arises from sporadic adenomatous polyps (75%)."

Tags:mismatch, repair, genes, enzymes, germline, mutation, adenoma, carcinoma