CDC Expert Commentary

Genetic Testing for Lynch Syndrome in Colorectal Cancer

W. David Dotson, PhD


February 07, 2011

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Hello, I am Dr. David Dotson from the Office of Public Health Genomics at the Centers for Disease Control and Prevention (CDC). I am speaking to you as part of the CDC Expert Commentary Series on Medscape

Today I'd like to share with you a recent evidence-based recommendation for genetic testing for Lynch syndrome in all persons with newly diagnosed colorectal cancer.

What Is Lynch Syndrome?

Lynch syndrome is a hereditary condition associated with colorectal cancer and other cancers. It is also referred to as hereditary nonpolyposis colorectal cancer (HNPCC). People with Lynch syndrome have a greatly increased chance of developing colorectal cancer, especially at ages younger than 50 years old. Approximately 3 out of every 100 people in the United States diagnosed with colorectal cancer have Lynch syndrome, or an estimated 4000 people per year.

Close biological relatives (such as parents, children, sisters, and brothers) of people with Lynch syndrome are at a 50% risk for also having Lynch syndrome. Other relatives, such as grandparents, aunts, uncles, nieces, and nephews, are also at risk.

What Evidence for Action Do We Have?

In 2009, the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group released a recommendation regarding genetic testing for Lynch syndrome in newly diagnosed patients with colorectal cancer. EGAPP is an independent group of scientists and healthcare experts who systematically review available research to make evidence-based recommendations about the use of genetic tests and other applications in clinical and public health practice. Although EGAPP is supported by CDC, EGAPP recommendations do not represent official positions of the agency.

The EGAPP Working Group found sufficient scientific evidence to recommend that all people with a new diagnosis of colorectal cancer (regardless of age or family history) be offered genetic testing for Lynch syndrome, in order to help prevent cancer in their close relatives.

What Are Some Considerations for Clinical Practice?

If your patient is found to carry a genetic mutation associated with Lynch syndrome, your patient's relatives can be tested to determine if they also carry the mutation. Relatives found to have a Lynch syndrome gene mutation can lower their chance of developing or dying from colorectal cancer by having earlier and more frequent colonoscopies: every 1-2 years, beginning at age 20-25 years. Colonoscopy every 1 to 2 years is also recommended for patients with newly diagnosed colorectal cancer who test positive for Lynch syndrome.

Family members who learn that they do not carry the mutation, on the other hand, are at no greater risk than the average person, and can adhere to the standard guidelines for colorectal cancer screening starting at age 50.

Several testing approaches are potentially effective for identifying Lynch syndrome.

Most current protocols are directed at screening all patients with colorectal cancer for Lynch by conducting preliminary testing of tumor tissue using microsatellite instability (or MSI) and/or immunohistochemistry (or IHC). These test results guide subsequent DNA analysis needed to diagnose Lynch syndrome by identifying mutations in mismatch repair genes. Although there are multiple approaches to preliminary testing, the EGAPP Working Group did not find sufficient evidence to recommend the use of one specific approach.

According to the EGAPP Working Group, patients newly diagnosed with colorectal cancer should be offered testing even if there are no other known family members with Lynch syndrome cancers. This is because family history identifies fewer people with Lynch syndrome than tumor testing strategies and because of the difficulty and cost of obtaining a reliable family history. However, family history may still be an important decision tool for identifying individuals in the general population who should be referred to genetic counseling services for the evaluation of their risk for hereditary colorectal cancer.

The EGAPP Working Group also recommends obtaining informed consent from the patient before MSI or IHC testing occurs, given that the testing of the patient is for the benefit of family members. The EGAPP Working Group found no substantial evidence that identifying Lynch syndrome through routine genetic testing leads to adverse psychological outcomes. They found that the available evidence suggests sufficiently high levels of counseling and testing uptake, as well as adherence to screening, to justify implementing routine genetic testing strategies among relatives if the patient is found to have Lynch syndrome.

As with any new clinical practice recommendation, much work remains with respect to how to most effectively implement these recommended practices. There is also a need for ongoing evaluation to monitor whether the recommended practices are having the intended health impact. A recent basic economic analysis has shown that genetic testing strategies for Lynch syndrome as recommended by the EGAPP Working Group are cost-effective; however, future studies will be helpful in further defining the societal costs of implementing widespread genetic testing in the colorectal cancer population.

In closing, the EGAPP Working Group recommends that all people with a new diagnosis of colorectal cancer be offered genetic testing for Lynch syndrome, in order to help prevent cancer in their close relatives. Fully implementing genetic testing for Lynch syndrome among all persons with newly diagnosed colorectal cancer could prevent thousands of colorectal cancers each year among the relatives of those patients found to have Lynch syndrome.

If you need additional information, links to the EGAPP recommendation and other resources are provided below.

Thank you.

Web Resources

Recommendations from the EGAPP Working Group: genetic testing strategies in newly diagnosed individuals with colorectal cancer aimed at reducing morbidity and mortality from Lynch syndrome in relatives.

EGAPP Summary of the EGAPP Recommendation

CDC Genetic Testing: Lynch Syndrome of the EGAPP Recommendation

Lynch Syndrome, Genetics Home Reference, US National Library of Medicine

Hereditary Non-Polyposis Colon Cancer, Gene Reviews

Clinic Directory, Gene Tests, National Center for Biology Information

Find a Genetic Counselor, National Society of Genetic Counselors

Cancer Genetics Services Directory, National Cancer Institute.

W. David Dotson, PhD, is health scientist in CDC's Office of Public Health Genomics (OPHG), which serves as the national focus for integration of genomics into public health research and programs for disease prevention and health promotion. Since joining OPHG in 2007, Dr. Dotson's efforts have focused primarily on contributing to (1) sustaining development of the EGAPP™ initiative to establish and test a systematic, evidence-based process for evaluating genetic tests and other applications of genomic technology that are in transition from research into clinical and public health practice; (2) establishing the Genomic Applications for Prevention and Practice Network (GAPPNet™) initiative to accelerate the effective translation and integration of genomic knowledge into the practice of medicine and public health; and (3) developing and editing a novel online publication forum that would go on to become PLoS Currents: Evidence on Genomic Tests.

Dr. Dotson began his career as a laboratory scientist, serving as a postdoctoral fellow in the biotechnology industry, and specializing in techniques for the analysis of gene expression. He has also worked as a senior medical writer in the pharmaceutical industry, where he focused largely on diabetes and its complications and developed a professional interest in chronic disease prevention and health promotion.

Dr. Dotson received his BS in Biochemistry and his PhD in Microbiology from North Carolina State University. In addition, he has earned a graduate certificate in Public Health from the University of North Carolina at Chapel Hill.


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