Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC), is the most common cause of hereditary colorectal (colon) cancer.

People with Lynch syndrome are more likely to get colorectal cancer and other cancers, and at a younger age (before 50), including

• Uterine (endometrial),
• Stomach,
• Liver,
• Kidney,
• Brain, and
• Certain types of skin cancers.

Lynch syndrome causes about 4,000 colorectal cancers and 1,800 uterine (endometrial) cancers per year.

Genetics and Lynch syndrome

Lynch syndrome is due to inherited changes (mutations) in genes that affect DNA mismatch repair, a process that fixes mistakes made when DNA is copied. These genes (MLHL, MSH2, MSH6, PMS2, and EPCAM) normally protect you from getting certain cancers, but some mutations in these genes prevent them from working properly.

Everyone has two copies of each of the genes involved in Lynch Syndrome, one from their mother and one from their father. Even if a person inherits a mutation in a Lynch syndrome gene, they still have the normal copy of the gene from the other parent. Cancer occurs when a second mutation affects the normal working copy of the gene, so that the person no longer has a copy of the gene that works properly. Unlike the inherited Lynch syndrome mutation, the second mutation would not be present throughout the person’s body, but would only be present in the cancer tissue. However, not everyone with Lynch syndrome will get cancer.

Colorectal cancer also can be caused by mutations in genes other than those related to Lynch syndrome. This means that some families with a history of colorectal cancer will not have mutations in a Lynch syndrome gene. These mutations might be picked up through genetic testing using multigene panels, which look for mutations in several different genes at the same time.

Family Health History is Important

You and your family members are more likely to have Lynch syndrome if your family has a strong history of colorectal cancer. Family members who inherit Lynch syndrome usually share the same mutation. If one of your family members has a known Lynch syndrome gene mutation, other family members who get genetic testing should be checked for that mutation.

If you are concerned that you could have Lynch syndrome, or another mutation related to colorectal cancer, the first step is to collect your family health history of colorectal cancer and share this information with your doctor.

Having a family health history of colorectal (colon) cancer can make you more likely to get colorectal cancer yourself. If you have close family members with colorectal cancer, collect your family health history of colorectal and other cancers, and share this information with your doctor. Be sure to have any screening tests that your doctor recommends. If you have had colorectal cancer, make sure that your family members know about your diagnosis, especially if you have Lynch syndrome.

Why is it Important to Know Your Family Health History?

If you have a family health history of colorectal cancer, your doctor may consider your family health history when deciding which colorectal cancer screening might be right for you. For example, if you have a close family member who had colorectal cancer at a young age or have multiple close family members with colorectal cancer, your doctor may recommend the following:

• start screening at a younger age,
• get screened more frequently,
• use colonoscopy only instead of other tests, and
• in some cases, have genetic counseling.

The genetic counselor may recommend genetic testing based on your family health history. When collecting your family health history, be sure to include your close relatives: parents, brothers, sisters, children, grandparents, aunts, uncles, nieces, and nephews. List any cancers that each relative had and at what age he or she was diagnosed. For relatives who have died, list age and cause of death. You can use the My Family Health Portrait tool to collect your family health history.

What is Lynch Syndrome and Why is it Important to Know if You Have it?

In some cases, colorectal cancer is caused by an inherited genetic condition called Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer or HNPCC. About 3% (1 in 30) of colorectal cancer cases are due to Lynch syndrome. People with Lynch syndrome are much more likely to develop colorectal cancer, especially at a younger age (before 50), and women with Lynch syndrome are much more likely to get endometrial (uterine) cancer. People with Lynch syndrome also have an increased chance of getting other cancers, including ovarian, stomach, liver, kidney, brain, and skin cancer. If you or your family members are found to have Lynch syndrome, your doctor can help you take steps to reduce your risk of getting cancer in the future or to find it early if you get it.

Lynch syndrome is hereditary, meaning that it is caused by an inherited genetic changes, or mutations, that can be passed from parents to children. If you have Lynch syndrome, your parents, children, sisters, and brothers have a 50% (1 in 2) chance of having this condition. Your other close relatives are also at increased risk of having Lynch syndrome.

After surgery to remove colorectal cancer, tumor tissue samples are often screened to see if the tumor could have been caused by Lynch syndrome. In some cases, additional testing is needed to know for sure if the tumor was caused by Lynch syndrome. If you have had colorectal cancer in the last few years, your tumor may have been checked for Lynch syndrome. In some cases, endometrial (uterine) tumors are checked. Genetic counseling and testing for Lynch syndrome also might be recommended for you if:

• You were diagnosed with colorectal cancer in the past
• You have been diagnosed with endometrial cancer (especially before age 50)
• You have several family members with colorectal or other cancers related with Lynch syndrome
• You have a family member with Lynch syndrome

If you have been diagnosed with Lynch syndrome, talk to your doctor about your increased chances of getting the other cancers caused by Lynch syndrome. Your doctor might recommend additional regular screening to check for these cancers or other actions you can take to prevent cancer. Be sure to let your family members know if you have Lynch syndrome. Once a mutation that causes Lynch syndrome is found in one person in a family, other family members can then be tested for that mutation to find out if they have Lynch syndrome.

If you are concerned about your personal or family health history of colorectal cancer, talk to your health care provider. In addition, you can visit the web sites below to find information on colorectal cancer, Lynch syndrome, cancer genetic testing, and genetic counseling services.

Genetic testing is available for Lynch syndrome. However, most colorectal cancer is not caused by inherited mutations, so Lynch syndrome testing will not benefit most people with a family health history of colorectal cancer who have not had cancer themselves. Genetic testing will not identify the cause for some hereditary colorectal cancers, because the genes affected in these cancers are not yet known.

Usually, genetic testing will be recommended if

• Your tumor screening results (IHC or MSI) are abnormal
• You have had colorectal cancer
• You had uterine (endometrial cancer) before age 50
• You have had multiple primary cancer diagnoses
• Several family members have had cancers related to Lynch syndrome
• You have a family member with Lynch syndrome

Genetic testing looks for inherited Lynch syndrome mutations. Your doctor may recommend a multi-gene panel, which looks for mutations in several genes at the same time, including the genes associated with Lynch syndrome.

The genetic counselor can help to determine the best testing strategy for you and your family. When possible, testing should start with someone in the family who has had cancer. However, if none of your family members who have had cancer are available for testing, genetic testing can start with an unaffected person.

Genetic Testing Results

Interpretation of genetic testing results may vary, depending on whether you have had colorectal cancer in the past or not.

If you have already colorectal cancer what the test results mean to you and your family

You have not had colorectal cancer what the test results mean to you and your family

Understanding and dealing with your own or family members’ colorectal cancer can be challenging. Genetic counseling can help by providing information, resources, and support for you and your family. Genetic counseling can help you better understand your likelihood of getting cancer and make an informed decision about what genetic testing option is best for you.

A genetic counselor or other health care provider with specialty training in cancer genetics can provide genetic counseling. Often getting counseling for Lynch syndrome is covered by insurance companies, but not always. Risk information obtained through genetic testing could potentially impact your insurance eligibility. A law called the Genetic Information Nondiscrimination Act prevents employers and health insurers for discriminating against people based on genetic test results. However, life insurance, disability insurance, and long term care insurance are not included under this law.

Your doctor may refer you for genetic counseling if you have

• Already had colorectal cancer
  • After surgery to remove colorectal cancer, tumor tissue samples are often screened to see if the tumor could have been caused by Lynch syndrome.
  • In some cases, additional testing is needed to know for sure if the cancer was caused by Lynch syndrome.
• A family member diagnosed with Lynch syndrome
  • Genetic counseling is recommended to see if testing for the Lynch syndrome mutation that runs in your family is right for you.
• A family history of colorectal cancer
  • Your doctor may recommend genetic counseling to see if the cancers in your family are caused by Lynch syndrome, especially if members of your family were diagnosed with colorectal cancer before age 50.
  • The first person tested in your family should be someone who has had colorectal cancer, if possible.

Genetic counseling can provide answers to questions like the following:

• Do you have an increased risk for colorectal cancer because of your family health history?
• What is the chance you have a Lynch syndrome gene mutation?
• Could the colorectal, or other cancers that runs in your family be due to mutations in genes other than the Lynch syndrome genes?
• If you have Lynch syndrome, or another hereditary cancer syndrome, how likely are you to get cancer?
• How will the results of genetic testing for colorectal cancer affect your family members?
• Who in your family should be the first to have genetic testing for Lynch syndrome?
• What are the possible results of genetic testing for Lynch syndrome and what do the results mean?
• What are the potential risks and limitations of genetic testing for Lynch syndrome?
• How will knowing you have Lynch syndrome help you lower your risks for cancer?
• If you have already had colorectal or other cancers, how will knowing if you have Lynch syndrome affect your treatment plan?
• If you have previously been treated for colorectal cancer, what are the chances you will get cancer again?

Following genetic counseling, you can decide whether you would like to have genetic testing done. If you decide to have genetic testing, additional genetic counseling following the testing can help you better understand your test results. The genetic counselor will be available to answer any questions you have regarding your results and your medical options.

Why talk to my family?

Your family members can benefit from knowing about your diagnosis of Lynch syndrome. Talk to your family members about Lynch syndrome, and tell them

• Lynch syndrome is passed through families

• A person with Lynch syndrome is more likely to get colorectal, endometrial (uterine), ovarian, and other cancers

• Genetic counseling and testing for Lynch syndrome can provide information about their risk

• They should be tested for the same mutation that you have if they choose to be tested

• They can take steps to prevent colorectal and other cancers or find them easier

How do I talk to my family about my Lynch syndrome diagnosis?

• WHO: Your parents, siblings, and children are the family members who are most likely to have Lynch syndrome (50% or 1 in 2 chance). Other blood relatives, such as aunts, uncles, nieces, nephews, and cousins, are also likely to have Lynch syndrome. Your healthcare provider or genetic counselor can help you figure out who in your family might have Lynch syndrome and thus would benefit from knowing about your diagnosis.
• WHAT: You can share test results, letters from your doctor or genetic counselor, or other information you received about your diagnosis with your family. Telling your family members about your specific genetic mutation helps their healthcare providers know exactly which test to use and might help save your family money.
• HOW: If you need extra support talking to your family, bring a friend. You can also ask a family member to attend your next medical appointment with you. You can also use this sample letter to fill out and send to your family.

How do I talk to my children?

If you have Lynch syndrome, each one of your children has a 1 in 2 (50%) chance of also having Lynch syndrome. Genetic testing for Lynch syndrome is typically not recommended for children younger than 18 but can be considered once your children reach adulthood.

Younger children may not understand what your diagnosis means for them. Children differ in the age at which they are ready to learn about this question. Answer any questions they ask, but know they will ask more complex questions as they grow older and are ready to learn more. Children may have fears about the risk to you and themselves. Just as you need time and support to cope with the information and accept it, your children will too.

What if my family does not want to talk?

Talking to some family members about Lync syndrome might not be easy. Some may be unsure of why they need to know this information. Others may be nervous about receiving a diagnosis of Lynch syndrome.

Remember that family members need to make their own choices about getting tested, whether or not you agree with their decisions. If family members do not want to discuss Lynch syndrome, respect their wishes. Let them know you are available to talk if they have questions and provide them with places to find information.

When family members do not want to talk about Lynch syndrome, you may feel upset or alone. Seek support from friends, healthcare providers, other family member or people you know with Lynch syndrome.

Cascade testing for Lynch syndrome can find family members who are more likely to get colorectal (colon), uterine (endometrial), ovarian, and other cancers. Knowing about their increased risk allows family members to take steps to prevent these cancers or find them early when treatments are more likely to be successful.

If you have been diagnosed with Lynch syndrome, your family members could also have it. Family members who decide to get genetic testing for Lynch syndrome should be checked for the same genetic change you have. Getting screened using a cancer test available for a variety of cancers might not include the genetic change that you have, so family members should talk to their doctors about making sure that their test includes your genetic change.

Ask your genetic counselor or other health care provider if the company that did your genetic testing offers free or discounted genetic testing to your at-risk family members. In some cases, free or discounted testing is only available for a limited amount of time after your initial test.

Current recommendations state that colorectal (colon) and some uterine (endometrial) tumors should be tested for Lynch syndrome. However, most people who get colorectal (colon) or uterine (endometrial) cancer do not have Lynch syndrome, so having a family member with these cancers does not necessarily mean that cascade testing is needed. A genetic counselor can help you decide if genetic testing is recommended.

What Are My Family Members’ Chances of Having Lynch Syndrome?

• Your mother, father, children, and siblings have a 1 in 2 (50%) chance of having Lynch syndrome.
• Your half-siblings, aunts, uncles, grandmothers, and grandfathers have a 1 in 4 (25%) chance of having Lynch syndrome.
• Your cousins and other more distantly related family members can have as much as a 1 in 8 (12.5%) chance of Lynch syndrome.

A health care provider, such as a genetic counselor, can help with personalized risk estimates for each person in your family.

Who Should Get Tested?

When possible, genetic testing should start with family members who are most closely related to the person diagnosed with Lynch syndrome. However, if a family member is not available for testing (for example, the family member does not want to be tested or has died), testing can start with more distant family members.

Because interventions for Lynch syndrome start in adulthood, most current guidelines recommend that testing for Lynch syndrome should only be done on adults (18 years of age and older). This allows children, rather than their parents, to make their own decision about genetic testing once they become adults. Talk to your genetic counselor or other health care provider about how to provide information to your children so they are empowered to make their own decision about genetic testing when the time is right.

How Do Family Members Get Tested?

The genetic counselor or health care provider who diagnosed you might be able to help schedule genetic counseling and testing for your family members. Provide your genetic test report to any genetic counselor or health care provider who orders testing for your family. If free or discounted cascade testing for family members is limited to a certain amount of time from the first genetic test report, they might need a copy of your report to show the date of your test. Some insurance companies will cover genetic testing for families if a known genetic change is found. A genetic counselor or health care provider can give more information on coverage with your specific insurance.