Lynch syndrome

Overview

Lynch syndrome is a genetic condition that raises the risk of many types of cancer, especially colon cancer and endometrial cancer. It's an inherited condition, which means it's passed down through families. Cancers caused by Lynch syndrome often occur earlier in life than they do in the general population.

Regular screening tests, such as colonoscopy and other exams, can find cancers early, when they are most treatable. Some people also may consider preventive surgery or medicines to lower their risk.

Lynch syndrome used to be called hereditary nonpolyposis colorectal cancer (HNPCC). HNPCC was a term used to describe the condition in families with a strong history of colon cancer, with or without colon polyps. Colon polyps are growths of extra tissue lining the colon. Early research divided HNPCC into two types:

• Type 1, involving colon cancer only.
• Type 2, involving colon cancer plus other cancers, such as uterine, ovarian or stomach cancer.

Today, these distinctions are no longer used. The term "Lynch syndrome" is now preferred, as it reflects the underlying genetic cause and recognizes that the syndrome increases the risk of several types of cancer, not just colon cancer.

Other related hereditary cancer syndromes

Several other inherited syndromes also can raise the risk of colon and other cancers, including:

• Familial adenomatous polyposis (FAP). FAP is an inherited condition that causes hundreds to thousands of polyps to form in the colon. These polyps have a very high chance of turning into cancer and often start developing in the colon in the teenage years. For people with FAP, if the colon isn't removed, there is a nearly 100% chance of developing colorectal cancer. For other people with a milder form of FAP, known as attenuated FAP, colorectal cancer might be prevented through careful colonoscopy surveillance and removal of polyps.
• Gardner syndrome. This is a type of FAP. Along with causing many colon polyps, it can cause noncancerous lumps on the skin, extra bone growth and soft tissue tumors in the body.
• Li-Fraumeni syndrome. This condition greatly increases the risk of many different cancers at a young age, including cancers of the breast, brain, bones and soft tissues. It is not related to the gene changes seen in Lynch syndrome.
• Muir-Torre syndrome. This is a rare form of Lynch syndrome. In addition to being at risk of the usual internal cancers, people with this condition may develop small skin tumors in oil glands, called sebaceous adenomas or sebaceous carcinomas.

Symptoms

Lynch syndrome usually doesn't cause symptoms until cancer develops. Because of this, many people feel healthy for years and only learn they have the condition after a family member is diagnosed.

When symptoms appear, they come from the cancer itself. For example:

• Colon cancer may cause blood in the stool, changes in bowel habits, belly pain or weight loss that happens without trying.
• Endometrial cancer may cause vaginal bleeding or pelvic pain that is not typical.
• Stomach or small bowel cancers may cause indigestion, nausea or unexplained anemia.
• Cancers of the urinary tract may cause blood in the urine.

People with Lynch syndrome also may develop cancer at younger ages than usual, or experience more than one type of cancer during their lifetimes.

Because early cancers may not cause clear symptoms, regular screening tests are the most reliable way to find and treat cancer early.

When to see a doctor

If a member of your family has Lynch syndrome, tell your healthcare professional. Ask to see a specialist in genetics, such as a genetic counselor. That person can help you understand Lynch syndrome, what causes it and whether genetic testing is right for you.

Causes

Lynch syndrome is caused by an inherited change, called a pathogenic variant or mutation, in one of five genes that repair DNA damage. These genes are called MLH1, MSH2, MSH6, PMS2 and EPCAM.

These genes are known as DNA mismatch repair (MMR) genes. Their job is to find and correct small copying errors in DNA. If one copy of an MMR gene is changed, the body can still repair DNA using the healthy copy. But if the healthy copy is later damaged or lost — for example, in a cell in the colon — then DNA errors begin to build up and can cause cells to grow out of control and become cancer.

If one parent has a gene mutation in one of the genes responsible for Lynch syndrome, there's a 50% chance that each biological child will inherit that mutation and have Lynch syndrome. This is called an autosomal dominant inheritance pattern.

Risk factors

You can develop Lynch syndrome only if you inherit a genetic change that affects one of the DNA repair genes: MLH1, MSH2, MSH6, PMS2 or EPCAM.

Your risk is higher if you have:

• A parent, sibling or child diagnosed with Lynch syndrome.
• A strong family history of early or multiple cancers linked to Lynch syndrome — including colon, endometrial and uterine cancers — before age 50.
• A known change in one of the mismatch repair (MMR) genes passed down in your family.

Lynch syndrome can occur in a family without a known history if the change in the gene happens for the first time. This is known as a de novo variant.

Complications

Lynch syndrome increases the lifetime risk of developing several types of cancer. These cancers associated with Lynch syndrome often occur at a younger age than in the general population.

Common cancers linked to Lynch syndrome include:

• Biliary system cancers, including cancer of the gallbladder and bile duct.
• Brain cancer.
• Digestive system cancers, including cancer of the stomach, small bowel and colon.
• Female reproductive system cancers, including endometrial, uterine and ovarian cancers.
• Pancreatic cancer.
• Skin cancer, particularly cancer that affects small glands in the skin that make oil, called sebaceous glands.
• Urinary system cancers, including cancer of the area at the center of the kidney, called the renal pelvis, as well as bladder cancer and cancer of the tubes that connect the kidneys to the bladder, called the ureters.
• Prostate cancer.

Current research hasn't shown a clear link between Lynch syndrome and an increased risk of breast cancer. Some breast cancers in people with Lynch syndrome show the same DNA repair gene changes, but experts agree there isn't enough evidence to consider breast cancer part of the Lynch syndrome cancer spectrum.

Diagnosis

A diagnosis of Lynch syndrome often starts by reviewing a family's history of cancer. Depending on that family history, various tests and procedures may be used to diagnose Lynch syndrome.

Family history

Your healthcare professional may advise genetic testing for Lynch syndrome if one or more of the following are true for you:

• More than one blood relative had any cancer that could be linked to Lynch syndrome, including colon cancer or endometrial cancer. Other cancers caused by Lynch syndrome include those that affect the stomach, ovaries, pancreas, brain, small intestine, ureters, gallbladder, bile duct, bladder and skin, as well as cancer that affects the area at the center of the kidney, called the renal pelvis.
• One or more blood relatives had a type of cancer related to Lynch syndrome before age 50.
• One or more blood relatives have had more than one type of cancer related to Lynch syndrome.
• More than one generation of your family has had the same kind of cancer.

Testing cancer cells

If you or someone in your family has had cancer, a sample of the cancer cells may be tested for Lynch syndrome.

Tests on cancer cells include:

• Immunohistochemistry (IHC) testing. IHC testing uses dye to stain the cancer cells. The staining shows whether the cells have certain proteins. Missing proteins may help the care team see whether genes related to Lynch syndrome caused the cancer.
• Microsatellite instability (MSI) testing. Microsatellites are pieces of DNA. In people with Lynch syndrome, there may be errors or issues in microsatellites.

Positive IHC or MSI test results can show that the cancer cells have genetic changes that are connected to Lynch syndrome. But the results don't tell for sure whether you have Lynch syndrome. Some people have these genetic changes only in their cancer cells. This means the genetic changes weren't passed down within a family.

People with Lynch syndrome have a specific change in the gene that causes Lynch syndrome in all the cells in their bodies. Genetic testing is needed to see whether all the cells have this change.

Genetic testing

Genetic testing looks for changes in the genes that can cause Lynch syndrome. The testing is often done with a sample of blood. But sometimes, genetic testing may be done with a sample of saliva or by using a swab to collect tissue from inside the cheek, called a buccal swab.

If a family member has Lynch syndrome, genetic testing may look only for the gene that runs in the family. If you're the first person in your family to be tested for Lynch syndrome, the test may look at many genes associated with Lynch syndrome. A genetics professional can help decide which test is best for you.

Genetic testing may show:

• A positive result. A positive genetic test result means a genetic change that causes Lynch syndrome was found in the cells. It doesn't mean you'll get cancer. But it does mean that your risk of some cancers is higher than it is in people who don't have Lynch syndrome.

  Your risk of cancer also may depend on which Lynch-related gene runs in your family. A genetics professional can explain your risk based on the genetic test results.

• A negative result. A negative genetic test result means gene changes that cause Lynch syndrome weren't found in the cells. It means you probably don't have Lynch syndrome. But you could still have a higher risk of getting cancer. That's because people with a strong family history of cancer may have a higher risk of the disease.
• An unclear result. Genetic tests don't always give a yes or no answer. Sometimes, genetic testing finds a gene change that healthcare professionals aren't sure about. This is called a variant of unknown significance. A genetics professional can help you understand what this type of test result could mean for your health.

At-home genetic testing

There are no reliable at-home testing kits for Lynch syndrome. At-home DNA tests can provide information about ancestry or general health traits, but they can't reliably detect Lynch syndrome. These mail-in kits usually check only a few common genetic markers and don't include the detailed testing needed to find changes in the MLH1, MSH2, MSH6, PMS2 or EPCAM genes that cause Lynch syndrome.

For accurate results, genetic testing should be done through a healthcare professional or genetic counselor, who can order a medical-grade test from a certified laboratory and interpret the results correctly.

Treatment

There's no cure for Lynch syndrome. People with Lynch syndrome often have tests to look for early signs of cancer. This is called cancer screening. If cancer is found early, when it's small, treatment is more likely to be successful. Sometimes the risk of cancer can be significantly lowered with surgery or other treatment.

Cancer screening

For people with Lynch syndrome, cancer screening tests are especially important because cancers can develop at a younger age and get worse more quickly than in the general population. The cancer screening tests you need depend on the Lynch syndrome gene you carry and what cancers run in your family.

Treatment to prevent cancer

In some situations, surgery or other treatment to reduce risk of cancer may be a good choice for people who have Lynch syndrome. Talk about the benefits and risks with your healthcare professional.

Treatment to reduce risk of cancer may be available for:

• Endometrial cancer. Surgery to remove the uterus is called a hysterectomy. It prevents endometrial cancer. Another option may be a procedure to place a birth control device in the uterus. The device, called an intrauterine device (IUD), releases a hormone that lowers the risk of endometrial cancer. An IUD also prevents pregnancy.
• Ovarian cancer. Surgery to remove the ovaries is called an oophorectomy. It greatly lowers the risk of ovarian cancer. Another option is taking oral contraceptives, also called birth control pills. Research suggests that taking birth control pills for at least five years lowers the risk of ovarian cancer.
• Colon cancer. Surgery to remove most or all of the colon is called a colectomy. It lowers the risk of colon cancer.

Aspirin for cancer prevention

Some research suggests that taking an aspirin every day may lower the risk of cancer in people with Lynch syndrome. Research shows that taking a baby aspirin daily is enough to help prevent colorectal cancer. Talk with your healthcare professional to decide whether taking aspirin could be a good choice for you.

Potential future treatments

There are no treatments that cure or reverse Lynch syndrome itself. This is because it is an inherited genetic condition. But researchers are studying new ways to prevent or treat cancers linked to Lynch syndrome:

• Cancer vaccines. Scientists are developing vaccines that teach the immune system to recognize and attack cells that are not typical before they turn into cancer.

  Early studies in people with Lynch syndrome show that these vaccines can safely trigger immune responses, but they are still being tested in clinical trials.

• Personalized or "precision" prevention. Researchers are learning that cancer risks vary depending on which Lynch-related gene is changed. Future care may use this genetic information to design prevention plans — such as when to start screening or how often to test — tailored to each person's exact gene mutation and family history.

Prognosis

People with Lynch syndrome have a higher chance of developing certain cancers at younger ages than most people, often before age 50. In the past, many were diagnosed only after symptoms appeared, leading to worse outcomes. Today, thanks to regular colonoscopies, endometrial screening and preventive surgeries, cancers are more often found early or prevented altogether. Most people who follow recommended care plans can expect a near-typical lifespan.

Coping and support

Learning you have Lynch syndrome can be stressful and may cause worry about your future. Over time, most people find ways to cope. Here are some practical steps that may help.

Learn about Lynch syndrome

Gather information so you can make informed decisions about your care. Write down your questions and bring them to your appointments. Ask your healthcare team for reliable resources. The more you know, the more confident you may feel about managing your health.

Take care of yourself

Focus on healthy habits you can control:

• Eat a balanced diet.
• Exercise regularly.
• Don't smoke.
• Limit alcohol.
• Maintain a healthy weight.
• Keep up with all medical appointments, including cancer screenings.

Find support

Talk with someone you trust about your feelings. This could be a friend, family member, counselor, social worker or clergy member. Ask a member of your healthcare team about support groups in your area. And find support online through Mayo Clinic Connect, which is an online community where you can connect with others for support, practical information and answers to everyday questions about your condition.

Addressing common concerns

Having Lynch syndrome may raise questions about other parts of your life, including:

• Privacy. You may worry about how your diagnosis could affect your insurance or job. A genetics professional can explain your legal protections.
• Children. If you have children or plan to, a genetics professional can help you understand inheritance, discuss genetic testing, and guide you on how and when to talk with your children about Lynch syndrome.
• Family. Lynch syndrome affects families. A genetics professional can help you plan conversations with blood relatives about risks and testing options.

Preparing for an appointment

Make an appointment with a healthcare professional if you have any symptoms that worry you. If your healthcare professional thinks you could have Lynch syndrome, you may be referred to a genetics professional, such as a genetic counselor.

A genetics professional can help you decide whether genetic testing would be useful for you. If you choose to have genetic testing, a genetics professional also can help you understand your results.

What you can do

To get ready for a meeting with a genetics professional:

• Gather your medical records. If you've had cancer, bring your medical records to your appointment.
• Ask for information from family members who've had cancer. If family members have had cancer, ask for information about their diagnoses. Write down the types of cancer they had, types of treatment and ages at diagnosis.
• Take a family member or friend along, if possible. Sometimes it can be hard to remember all the information provided during an appointment. Someone who comes with you may remember something that you missed or forgot.
• Write down questions to ask your care team.

Questions to ask

Examples of questions to ask a genetics professional include:

• What causes Lynch syndrome?
• How is Lynch syndrome passed through families?
• If I have a family member with Lynch syndrome, what is the chance that I have the syndrome too?
• What types of tests are involved in genetic testing?
• What will the results of genetic testing tell me?
• How long can I expect to wait for my results?
• If my genetic test result is positive, what is the chance that I will get cancer?
• What tests can find cancers at an early stage?
• If my genetic test result is negative, does that mean I won't get cancer?
• Are genetic testing results ever wrong or not clear?
• What do my genetic test results mean for my family?
• How much does genetic testing cost?
• Will my insurance company pay for genetic testing?
• What laws protect me from discrimination if my genetic test result is positive?
• Is it OK to decide against genetic testing?
• If I choose not to have genetic testing, what does that mean for my future health?
• Are there brochures or other printed material that I can take with me? What websites do you suggest?

Be sure to ask any other questions that you may have.

What to expect

The genetics professional will likely ask questions about your health history and the health history of your family. Questions may include:

• Have you ever had cancer?
• Have members of your family had cancer?
• At what age was each family member with cancer diagnosed?
• Have any family members ever had genetic testing?