Improving the Identification of Lynch Syndrome

Posted on February 5th, 2009 by

Lynch Syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC), results from inherited mutations in genes involved in DNA mismatch repair[1]These mutations greatly increase the risk of developing colorectal cancer and also increase the risk of several other cancers.

Average age at diagnosis of colorectal cancer is 44 years in individuals with an HNPCC mutation, compared to 64 years in the general population. Other cancers that are more common in HNPCC families include cancers of the endometrium (the lining of the uterus), ovary, small intestine, ureter, and renal pelvis. 

Overall, roughly 3% to 5% of all colorectal cancers are thought to result from HNPCC mutations. Although tools have been developed to identify individuals who are most likely to carry HNPCC mutations, limitations in these approaches have prompted researchers to search for more accurate methods. Accurate prediction of the likelihood of carrying an HNPCC mutation will allow for focused use of genetic testing.

Three recent studies reported on new approaches to identifying individuals who are most likely to carry an HNPCC mutation.

Two of these studies developed new statistical tools that estimate the probability that an individual carries an HNPCC mutation. [2],[3] These tools consider factors such as personal and family history of colorectal and endometrial cancers. Although the tools were developed in different populations and were not directly compared to each other, the overall accuracy of each appeared to be similar. Furthermore, they appeared to be more accurate than other commonly used approaches to estimating HNPCC risk.

The third study, conducted in Italy, reported on a novel indicator of HNPCC risk—the way in which light reflects of off tissues in the mouth. [4] Interest in this question was prompted by a report of vascular changes in the mouths of an HNPCC family.

The study enrolled 20 individuals from HNPCC families and 30 healthy comparison subjects. Light reflectance from tissues in the mouth was measured using an imaging spectrophotometer.

At particular wavelengths of light (590-700 nm), HNPCC family members showed less light reflection than the comparison subjects.

The researchers conclude that evaluation of how light reflects from tissues in the mouth may help in the identification of individuals and families who are at risk for HNPCC. The researchers note that “Further studies are needed in order to validate this new marker in identifying a susceptibility to [colorectal cancer] and to investigate its clinical utility in first level [colorectal cancer] screening programs.”

Use of these and other similar approaches may eventually improve the identification of individuals who could benefit from genetic testing for an HNPCC mutation. It is important to note, however, that many factors contribute to decisions about genetic testing. Genetic counselors and other health professionals can help patients understand the risks and benefits of genetic testing.


[1] National Cancer Institute. Genetics of Colorectal Cancer (PDQ®). Health Professional Version. (Accessed November 29, 2006).

[2] Balmana J, Stockwell DH, Steyerberg EW et al. Prediction of MLH1 and MSH2 Mutations in Lynch Syndrome. JAMA. 2006;296:1469-1478.

[3] Chen S, Wang W, Lee L et al. Prediction of Germline Mutations and Cancer Risk in the Lynch Syndrome. JAMA. 2006;296:1479-1487.

[4] De Felice C, Gentile M, Barducci A et al. Abnormal Oral Mucosal Light Reflectance: A New Clinical Marker of High Risk for Colorectal Cancer. Gut. 2006; 55:1436-1439.

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Tags: Colon Cancer

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