Lynch Syndrome is the most common form of hereditary colorectal cancer, with over 1.2 million people in the US currently diagnosed.

Up to 3-5% of all colorectal cancer is due to Lynch syndrome.

Unfortunately, this hereditary cancer is highly underdiagnosed – it is estimated that 95% of people who have Lynch don’t know they have it.

Quick Facts:

  • 50-80% lifetime risk of colorectal cancer
  • Many with Lynch syndrome are often diagnosed at an earlier age (Under 50)
  • Multiple generations on one side of the family (great-grandparent, grandparent, parent, aunt/uncle, child) often have cancer
  • “Clustering” of certain cancers in the family and higher risk of certain cancers
  • Individuals in the family may have more than one cancer

The Genes of Lynch syndrome

There are four “repair” genes that can be involved with Lynch syndrome, and one gene that can indirectly cause it:

  •  MSH2
  • MSH6
  • MLH1
  • PMS2

The gene EPCAM (formerly, TACSTD1) can ‘turn off’ the MSH2 gene, therefore leading to this cancer syndrome.

MMR genes

The genes are in a class called mismatch repair (MMR) genes.

MMR genes are like “spell checkers.”

Every time your body needs to make a new cell (which happens frequently!), it has to copy all of your genetic material exactly.

The MMR genes “spell check” the new copy of DNA to identify if any mistakes were made while it was being copied and then they repair those mistakes.

If the MMR genes are not working properly, these mistakes cannot be repaired and the new cell will have an abnormal copy of its genetic material.

When any one cell accumulates enough mistakes in its genetic material, it may start to grow out of control and not die when it should.

That cell can become a cancer.

High Cancer Risk

If you have Lynch syndrome, you are at higher risk for the following cancers:

  • Colorectal
  • Endometrial (uterine)
  • Stomach
  • Ovarian
  • Bladder
  • Liver
  • Kidney
  • Brain
  • Skin
  • Prostate
  • Pancreatic
  • Breast

Testing for Lynch syndrome

If your family history is suspicious of Lynch syndrome, genetic counseling and testing are recommended.

Many institutions now perform a screening test on all colorectal cancers and endometrial (uterine) tumors at the time of surgery that can determine whether you are more or less likely to have Lynch syndrome.

If you’re not sure this test was done, ask your oncologist.

If your surgery was not too long ago, it’s likely the test can still be performed.

Most hospitals perform one of these two screening tests, if not both:

Microsatellite instability (MSI)

MSI is a screening test that looks for changes in the DNA sequence between normal tissue and tumor tissue.

Defects in the MMR genes result in an increased accumulation of DNA errors, and stretches of DNA called microsatellites are especially prone to these errors.

Interestingly, 77-89% of Lynch-related tumors show MSI, but 10-15% of sporadic tumors also show it.

Given that both Lynch and sporadic tumors can show MSI, additional testing is needed to determine if it is truly Lynch syndrome.

MSI testing identifies if a tumor is MSI-H.

Immunohistochemistry (IHC)

Immunohistochemistry (IHC) testing is a screening test for Lynch syndrome which looks for missing proteins in tumor cells.

The premise behind the test is that if the MMR genes are working properly, their protein products should be present in the tumor.

However, if there is a mutation in one of the Lynch syndrome MMR genes, that gene’s protein will be absent in the tumor.

83-90% of Lynch-related tumors and 20% of sporadic tumors have at least one of these proteins absent.

IHC testing looks to see if there are missing proteins, which are made by MMR genes.

How do I understand the test results?

If the test is abnormal, you are more likely to have Lynch syndrome.

This would need to be determined by doing genetic testing for the Lynch syndrome genes.

If the test is normal, you are less likely to have Lynch syndrome, but it cannot be ruled out entirely.

What if I have Lynch syndrome?

Fortunately, there are many resources available for patients with Lynch syndrome.

This includes CRC patients as well as “previvors” – those who carry the genetic mutation but have not been diagnosed with a cancer.

Screening and Prevention Guidelines

If you have Lynch syndrome, your screening and prevention guidelines are different than the average-risk population, and you may have additional procedures:

  • Colonoscopy – every 1-2 years
  • Upper Endoscopy – every 1-3 years if you have a family history of stomach cancer or are of Asian ancestry
  • Urine cytology
  • Transvaginal ultrasound annually to check uterus/ovaries
  • Physical Exam – yearly
  • Removal of colon (colectomy) at the time of colon cancer diagnosis
  • Removal of uterus (hysterectomy) once childbearing is complete (around age 35-40)
  • Removal of ovaries (oopherectomy) once childbearing is complete (around age 35-40)
  • Medications to reduce polyp risk

Learn more about colorectal cancer screening for Lynch syndrome patients.

Treatment Options for Lynch syndrome Patients

Recent studies show immunotherapy may be an effective approach to treat patients who have CRC with MSI.

Therefore, knowing your MSI status could drastically change your treatment plan!

It is generally safe to assume that someone with one of the proteins missing on the IHC test has a tumor with MSI.

More Resources

Learn more about Lynch syndrome from our partners at ThinkGenetic.