What to know about Lynch syndrome, an inherited genetic disorder

Lynch Syndrome (LS) is a hereditary genetic disorder that greatly increases a person’s risk for cancer – mainly colorectal and endometrial (uterine) cancer, but also ovarian, stomach and other forms of the disease. People with LS also tend to be diagnosed with cancer at an earlier age than people in the general population.

So, how can you determine whether you have Lynch syndrome and what to do next, if you do have it? As a genetic counselor, I’ll explain.

What causes Lynch syndrome, and how is it inherited?

Every cell in our body contains thousands of genes that are made up of DNA, inherited information that acts as instructions for helping our bodies function properly. Any difference in this genetic information – called a pathogenic variant or mutation – can cause the gene to malfunction or stop working.

LS is caused by a pathogenic variant in one of five genes – MLH1, MLH2, MSH6, PMS2 or EPCAM – that are involved in repairing mistakes in our DNA that can occur during the body’s natural cell-division process. If you’ve inherited a pathogenic variant in one of those five genes, your body can’t properly repair DNA, increasing your risk for developing cancer. This is known as Lynch syndrome, named for the late Henry T. Lynch, MD, a geneticist whose work helped identify hereditary causes of cancer.

Who’s likely to have Lynch syndrome

There are multiple ways you might know if you are more or less likely to have LS.

If you’ve had cancer:

If you’ve had cancer, a screening test for LS might be performed on the cancerous tissue that was removed from you with a biopsy or surgery. These tests are called microsatellite instability (MSI) testing and immunohistochemistry (IHC) testing. Either or both tests can be performed on a tumor sample from a person suspected of having LS, and they’re often performed prior to testing for specific genetic variations.

MSI refers to changes in areas of DNA called microsatellites. The majority of colorectal and many uterine cancers stemming from LS are MSI-positive, so a diagnosis of LS is more likely if a person’s colon or uterine tumor is MSI-positive.

In IHC testing, special stains can show whether proteins made by LS genes are present in the tumor. If someone has an LS gene mutation, that gene’s protein will usually be absent in the tumor. IHC can help direct genetic testing so that only one of the five LS genes may need to be tested.

If you haven’t had cancer:

Even if you have not had cancer, details about your family history may help determine how likely you are to have LS. Most – but not all – people with LS have a significant family history of cancer. A cancer genetic counselor can review your family history information, estimate your likelihood of testing positive for LS or other hereditary cancer risk, and review your options for testing. The genetic counselor will ask you questions about who in your family has had cancer, what type they had and how old they were when they were diagnosed.

How genetic counselors help understand genetic risk and testing results

At Ohio State, we have one of the largest cancer genetic counseling groups in the nation, with 16 genetic counselors who support the cancer program and specialize in specific types of cancer. For example, I see our uterine cancer patients with LS. I also specialize in cascade testing, and I conduct research on developing communication strategies that help family members better share genetic information with each other.

How can I be tested to see if I have Lynch syndrome?

Genetic testing for LS is performed by laboratories using a blood or saliva sample to search for pathogenic variants in the LS genes. Once a pathogenic variant has been found in an LS gene, the lab can look for that same variant in other family members to see if they also have LS.

Since multiple genes are involved in LS, it’s most cost-effective to test all of them simultaneously in what we call a gene panel. Researchers at the OSUCCC – James have tested a one-step gene panel screening process that enables us to determine whether someone has an LS mutation while also screening for other gene mutations associated with cancer.

This kind of testing can be ordered by your doctor or a genetic counselor.

This process produces results faster and more accurately than the previous standard screening process, which could involve up to six tests. To determine the effectiveness of panel testing, OSUCCC – James researchers used gene sequencing to examine 419 unselected tumor samples in addition to 46 tumors from patients known to have LS and accurately identified 100% of the LS cases. The previous standard screening process for LS identified only 90% of the cases.

How does Lynch syndrome affect multiple members of the same family?

If your parent has Lynch syndrome, you have a 50% chance of inheriting LS and the associated increased likelihood of developing certain cancers. Likewise, if you have LS, each of your children has a 50% chance of also inheriting LS.

If you have discovered that you have LS, the next step is to share this information with as many family members as possible, so that they also can be tested for LS, too. This is called cascade testing, and it’s extremely beneficial in helping people guard against certain cancers through screening and promotion of early detection.

The Ohio State Genomic Health research study offers no-cost genetic screening

Cancer screening recommendations and risk-reducing strategies for people with Lynch syndrome

Regular colonoscopies

People who have Lynch syndrome have several choices. At a minimum, they should have screenings to help find cancers at the earliest possible stage. For colorectal cancer, this means a colonoscopy on a more frequent schedule to detect and remove precancerous polyps or to diagnose cancers early, when they can be more easily treated. Some people with LS are recommended to have colonoscopy every year, while others may have colonoscopy every few years.

Annual uterine cancer screenings

In people with LS who have uteruses, an annual pelvic examination, ultrasound and small biopsies of the uterus can be considered to screen for uterine cancer.

Optional surgery to lower risk

Some people with LS choose to consider a surgery to remove at-risk body parts before cancer develops, such as a hysterectomy (removal of the uterus) after the person is done having children. Risk-reducing colectomy (removal of the colon) is usually considered only when a person is unable to follow the LS colonoscopy screening recommendation.

Over-the-counter medication

Aspirin can be used to lower colon cancer risk in some people. You should discuss potential aspirin use with a physician. The decision to use aspirin for reduction of colorectal cancer risk in Lynch syndrome and the dose chosen should be made on an individual basis, including discussion of individual risks, benefits, adverse effects and childbearing plans.

How Lynch syndrome screening benefits patients and their families

Over $4 million in funding from Pelotonia, the annual cycling event that raises millions of dollars for cancer research at Ohio State, supported a five-year statewide initiative to screen newly diagnosed colorectal cancer patients and their biological relatives for LS via a network of 50 community hospitals around Ohio. This study enrolled over 3,300 patients, of whom 143 tested positive for LS. Through subsequent screenings, over 200 of these patients’ relatives also tested positive for LS, and more than 100 colorectal cancer patients were found to have a hereditary cancer syndrome other than LS.

Our findings clearly demonstrated the value of screening early-onset colorectal patients for LS and their family members, and we are working to help launch this screening approach nationally. One of the major advantages of learning LS test results is reduced uncertainty about the risks of cancer and being able to take precautions for avoiding it. In addition, testing may allow doctors to modify medical care to decrease the risk of all LS-associated cancers.