Dr. Carol A. Burke

Lynch Syndrome Awareness Day

Today, March 22nd, is Lynch Syndrome Awareness Day!

Up to about 1 million Americans are estimated to live with Lynch Syndrome (LS), and it is believed that 500,000 LS carriers have no idea they are at risk of disease.

As gastroenterologists know, LS is the most common inherited colorectal cancer syndrome. It accounts for three to five percent of all cases of colorectal cancer and 10 to 15 percent of colorectal cancers diagnosed in patients younger than age 50.

Did you know that LS is also the most common inherited cause of endometrial cancer? It causes up to three percent of all endometrial cancers.

On Lynch Syndrome Awareness Day, we should redouble our efforts to create opportunities in our practice to make a proactive diagnosis of LS by:

  • utilizing simple and directed family cancer history taking,
  • ensuring that all colorectal cancers in our patients are tested for evidence of microsatellite instability, a hallmark of LS,
  • seeing that appropriate patients and families are offered genetic testing, and
  • providing them with the education and management schema to prevent death from LS-related cancers.

Lynch Syndrome Q&A

What is Lynch Syndrome?

LS is an autosomal dominant hereditary cancer syndrome. It is caused by a germline mutation in one of the DNA mismatch repair (MMR) or EPCAM gene. LS is by definition a patient who has a germline LS mutation. LS should not be confused or used interchangeably with the term HNPCC. HNPCC is the term used to identify families who meet family cancer clinical criteria without regard to the molecular-genetic genesis of the cancer in the family.

LS should not be confused or used interchangeably with the term HNPCC. HNPCC is the term used to identify families who meet family cancer clinical criteria without regard to the molecular-genetic genesis of the cancer in the family.

Why care about LS?

Individuals with LS have a substantially increased lifetime cumulative risk of colorectal cancer and other LS-associated cancers including endometrial, ovarian, gastric, small bowel and urothelial tract. Prevention of the occurrence and death from some of these cancers due to LS is possible with recognition of the syndrome and preventive strategies, such as colonoscopy and prophylactic surgery.

Importantly, LS affects families. Once LS is diagnosed by genetic testing in one relative, other at-risk family members can undergo genetic testing and be offered appropriate management to decrease their risk of cancer.

How do I recognize LS?

One way to be suspicious of LS is by taking a family history. Historic family history criteria called Amsterdam I and II criteria include at least three relatives with CRC or other LS-associated cancer, affecting two successive generations of relatives, with one affected relative being less than age 50 and a first degree relative to two other affected relatives.

Dr. Burke and Jill Chang, of Lynch Syndrome International, hold a proclamation signed by Ohio Governor John Kasich declaring March 22 Lynch Syndrome Awareness Day in Ohio.

The recent U.S. Multi-Society Task Force (MSTF) colorectal cancer guideline on Lynch Syndrome
(Am J Gastroenterol 2014;109:1159-1179) reviews the clinical criteria and reminds us of a three-question checklist that can be used in the office or at the time of endoscopy to identify patients who should have a risk assessment for LS (Am J Gastroenterol 2009;104:1508-1518).

However, data show that the family history is not accurate enough to select which patients should be tested for LS. Some studies have shown that up to 40 percent of patients with LS do not meet clinical criteria for the syndrome (N Engl J Med 2005; 352:1851-60). In addition, up to 50 percent of families that meet the Amsterdam criteria for HNPCC do not have LS and their cause of cancer is unknown. The distinction is important as these families are managed differently. Molecular and genetic testing is required to make the diagnosis of LS.

Should I have my pathology laboratory test all colorectal cancers for LS?

Yes. Currently the national recommendation is that all colorectal cancer tumors should be tested for evidence of MMR deficiency. This is called “universal testing” and is endorsed by many organizations and agencies. Nearly all LS colorectal cancer shows high levels of microsatellite instability (MSI-H) or loss of expression of the MMR proteins on immunochemical stains (IHC) of the tumor. Clinicians must be aware that 80 percent of MSI-H tumors are due to sporadic colorectal cancers, which arise from sessile serrated polyps, and that the balance are nearly all due to LS.

How do I confirm the MSI-H and abnormal tumor IHC is caused by LS?

The diagnosis of LS is given to a patient who has a germline mutation in one of the MMR or EPCAM genes. Germline genetic testing is guided by the results of the CRC tumor IHC testing. Many commercial laboratories offer genetic testing for LS. Genetic counselors are invaluable in the process of risk assessment and providing genetic testing. The National Society of Genetic Counselors can provide information for a genetic counselor in your area (www.nsgc.org).

What is the role of a genetic counselor?

Genetic counselors are licensed practitioners. They perform a hereditary cancer risk assessment, provide patient and families education about hereditary causes of cancer, review the implications and cost of genetic testing, assure informed consent is obtained before testing, and devise a results disclosure plan. Old data showed that 32 percent of physicians misinterpreted the results of APC genetic testing for FAP (N Engl J Med 1997; 336:823-7.)

How do I manage the LS patient?

Once the diagnosis of LS is confirmed in your patient, offer testing as recommended by the MSTF and ACG guidelines (Am J Gastroenterol 2015;110:223–262) for their cancer prevention management.

Finally, be sure your patient knows that Lynch Syndrome is a family business and provide them recommendations to share with their family members, a lifesaving gesture!

Physician Resources

  • Kastrinos F, Allen JI, Stockwell DH, Stoffel EM, Cook EF, Mutinga ML, Balmaña J, Syngal S. Development and validation of a colon cancer risk assessment tool for patients undergoing colonoscopy. Am J Gastroenterol 2009 Jun; 104(6):1508-18. doi: 10.1038/ajg.2009.135. Epub 2009 Apr 28. Access this resource.
  • Giardiello FM, Allen JI, Axilbund JE, Boland CR, Burke CA, Burt RW, Church JM, Dominitz JA, Johnson DA, Kaltenbach T, Levin TR, Lieberman DA, Robertson DJ, Syngal S, Rex DK. Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US Multi-society Task Force on colorectal cancer. Am J Gastroenterol 2014 Aug; 109(8):1159-79. doi: 10.1038/ajg.2014.186. Epub 2014 Jul 22. Access this resource.
  • Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW; American College of Gastroenterology. ACG clinical guideline: genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol 2015; 110:223–262; doi: 10.1038/ajg.2014.435; Epub 2015 Feb 3. Access this resource.

— Carol