Screening Tumors for Lynch Syndrome is Cost-Effective

Screening all new colon and rectal cancer tumors for markers that might indicate Lynch syndrome not only saves future lives, it is cost effective according to a new study.

In order for tumor screening to be cost-effective, not only should new tumors be tested, but family members need to follow through with genetic testing after a new Lynch mutation is found.  Finally people with Lynch syndrome mutations need to follow surveillance guidelines to prevent cancer or find it early,

Testing both tumors and at least three to four family members could cost as little of $36,000 per life year saved — well within the value of preventive health strategies.

Researchers used a computer model to predict costs of  testing tumors using several strategies, upper age limits, and assumptions about family members following up with genetic testing.

In order to fall beneath the $50,000 per life year saved threshold for cost-effectiveness, three to four family members needed to follow up with DNA testing for an identified Lynch syndrome mutation.

Women with Lynch syndrome could improve their life expectancy by about four years if they had their uterus and ovaries removed and followed the colorectal cancer surveillance guidelines, the study found.

The researcher team said that the ideal testing strategy was for pathologists to:

  1. Use immunohistochemistry (IHC) tumor tests to look for missing protein expression  related to Lynch syndrome (MLH1, MSH2,MSH6, PMS2).
  2. If IHC is positive, followup with tumor tests for a BRAF V600E  mutation.  (Inherited Lynch mutations don’t have BRAF mutations.)
  3. If IHC is positive and BRAF is negative, do DNA blood tests for an inherited germline Lynch syndrome mutation.

Once an individual is identified with an inherited Lynch syndrome mutation, it is critical to inform close family members — siblings, children, and parents — of their own potential risk.  Since Lynch syndrome is passed directly from parent to child (autosomal dominant), children of an affected parent have a 50-50 chance of inheriting the gene.

When they know they are at risk, family members should also have DNA testing.  However, they only need to be tested for the gene discovered in their family — a much less expensive process.  Genetic counseling after their test can help them understand what the test results mean and, if positive, what steps they can take to protect themselves against cancer.

Study leader, Uri Ladabaum, M.D., from Stanford University, said,

A systematic approach to identify families with Lynch syndrome makes sense clinically, because it can save lives, and economically, because its costs are comparable to other things we choose to spend our health-care dollars on, We advocate establishing similar tumor-screening systems on a national level.

The study team, led by Dr. Ladabaum, included members from Stanford, University of California, Baylor University, and Memorial Sloan Kettering Cancer Center.  They concluded,

Widespread colorectal tumor testing to identify families with the Lynch syndrome could yield substantial benefits at acceptable costs, particularly for women with a mutation associated with the Lynch syndrome who begin regular screening and have risk-reducing surgery. The cost-effectiveness of such testing depends on the participation rate among relatives at risk for the Lynch syndrome.

Although family history can help identify individuals and families that may carry a Lynch syndrome mutation, it is not foolproof.  About half of families with mutations don’t meet the criteria and another half who do have histories that meet Amsterdam criteria don’t have one of the identified Lynch mutations.

In an editorial accompanying the study report in Annals of Internal Medicine, Dr. Randall Burt  from the University of Utah and the Huntsman Cancer Center points out:

The Amsterdam criteria were developed to identify persons and families who are likely to have the syndrome. The criteria include the following: 3 relatives in a family must have colorectal cancer, and 2 of them must be first-degree relatives of the third; at least 2 generations must be affected; and 1 of the cases must be diagnosed at an age younger than 50 years (2). These criteria have been successfully used to identify families with the Lynch syndrome but have also proven to be insensitive. At least 50% of families with the condition do not meet the criteria. About one half of families meeting the criteria will have a disease-causing mutation in one of the mismatch repair genes ( MLH1, MSH2, MSH6, or PMS2).

The Annals of Internal Medicine includes a summary for patients that describes the study and what it means.


Ladabaum et al., Annals of Internal Medicine, Volume 155, Number 2,  July 19, 2011.

Burt, Annals of Internal Medicine, Volume 155, Number 2,  July 19, 2011.

What This Means for Patients

This study looks at how costly a testing strategy to identify people with Lynch syndrome is for a large population.  The cost isn’t for one individual or one family, but for everyone in a national health care system.

However, it does support the idea that people who have surgery for colon or rectal cancer should have simple, inexpensive tests done on their tumor tissue to see if they might have Lynch syndrome.

This not a definitive test for Lynch syndrome.  It will also be positive for people who don’t have Lynch, but it will also screen and find those who do.

About 15 out of 100 of people with colon or rectal cancer will have tumors that suggest Lynch syndrome, but only 3 to 5 of them will actually carry a Lynch mutation.

Many of these people with Lynch mutations won’t have strong family cancer histories, so tumor testing is the only way the syndrome would be uncovered.

If you have had surgery to remove a colon or rectal tumor, check with  your doctor to see if testing for microsatellite instability (MSI) has been done.  It will be part of the pathology report from the surgical specimen.  Many hospitals are now doing this test automatically after surgery at the same time they look for lymph nodes and other tumor information.

If it wasn’t done, you might want to request it.  The tumor block saved by the pathology department should still be available for the test.

If testing does indicate you might carry a Lynch mutation, you’ll want to talk to a genetic counselor about DNA testing to either confirm or rule out Lynch syndrome.

The test can save your life by changing the way your cancer is followed up.  And it can save the lives of your brothers, sisters, and children if they also have the mutation.




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