This page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison.
Popular Press Review of "Strategies for Identifying Hereditary Nonpolyposis Colon Cancer" [1]
_ The diagnosis of HNPCC is an immense challenge because HNPCC patients do not present distinct symptoms but nevertheless have as high lifetime risk of developing cancers. [2] Recognition of HNPCC is important so that targeted screening can be effected that will reduce the incidence of the main cancers. Dr. D. Gareth Evans, Professor in Medical Genetics at St. Mary’s Hospital in Manchester, UK, and colleagues wrote an article discussing the situation. The article notes that family history has traditionally been used to categorize families high-risk for HNPCC. Although a family history is useful, it lacks sensitivity and fails to diagnose many patients with HNPCC. As such, Dr. Evans discusses the strategies other than family history that need to be applied to fully diagnose HNPCC.
HNPCC has been linked to mutations in msh-2 and mlh-1, genes that are part of the body's DNA repair system and responsible for correcting errors that occur during DNA replication. Sensitive techniques to detect these mutations are available and are the ultimate diagnostic tests for HNPCC; however, they are very expensive. [3] Other helpful techniques that are easier and cheaper to conduct can be applied. Mutations in either msh-2 or mlh-1 can cause specific regions of DNA to be altered by repetitive sequences. Testing for these repetitive sequence alterations, physicians can infer the presence of a mutation in either msh-2 or mlh-1. Furthermore, mutations in the msh-2 or mlh-1 genes would most likely result in no MSH-2 or MLH-1 protein produced. Testing for the presence of MSH-2 and MLH-1 proteins can help physicians determine whether mutations in these genes are present.
Selection of patients for testing for mutations in msh-2 and mlh-1 genes is a vital step to identifying individuals at high-risk of developing cancers due to HNPCC. A number of selection strategies are being employed, and none so far have proven to be superior over the others. Given the cost of testing for mutations in msh-2 and mlh-2, Dr. Evans suggests that pre-screening of selected patients with the other cheaper techniques mentioned may be the best current approach.
References 1. D. Gareth Evans, Sheila Walsh, James Hill, and Raymond T. McMahon, (2007) Strategies for Identifying Hereditary Nonpolyposis Colon Cancer. Semin Oncol., 34:411-417. 2. Schoen RE, (2000) Families at risk for colorectal cancer.J Clin Gastroenterol, 31:114-120. 3. Evans DG, Lalloo F, Mak A, et al. (2006) Is it time to abandon microsatellite instability as a pre-screen for selecting families for mutation testing for mismatch repair genes?J Clin Oncol. 24:1960-1962.