Frequently Asked Questions about Lynch Syndrome

What is Lynch syndrome?

A syndrome is a group of features that often occur together. Lynch syndrome, also called hereditary nonpolyposis colorectal cancer (HNPCC), is one of the most common hereditary cancer syndromes. A person with Lynch syndrome has an increased risk to develop colon or rectal cancer (which usually develops from a polyp called an adenoma). There is also an increased risk for cancers of the endometrium (uterus), ovary, stomach, small intestine, pancreas and upper urinary tract. If a person inherits a mutation in one of the Lynch syndrome genes (MLH1, MSH2, MSH6, PMS2, or EPCAM), he or she has Lynch syndrome and the associated cancer risks. These genes are also called mismatch repair genes because they repair specific types of damaged DNA within our cells.

There are some distinct variations of Lynch syndrome that include other features in addition to increased risks for colorectal and other cancers.

  • Muir-Torre syndrome is associated with the usual Lynch syndrome associated cancers and certain sebaceous gland lesions on the skin. 
  • Turcot syndrome is associated with colorectal cancer or colorectal polyps (adenomas) and a type of brain tumor called glioblastoma.
  • Constitutional Mismatch Repair Deficiency (CMMR-D) syndrome has been associated with childhood leukemia, brain cancer, and colorectal cancer. People with CMMR-D often have multiple large brown spots on the skin (known as café-au-lait spots). CMMR-D is unique because people with this syndrome carry mutations in both copies of one of the Lynch syndrome genes (one from each parent) whereas people with typical Lynch syndrome only carry 1 mutation (from just one parent).

The age and type of cancers can vary among people who have Lynch syndrome, even within the same family. It is important to know that many of the cancers seen in Lynch Syndrome families, like colorectal cancer, are also common in the general population. Most of the time, people with these common cancers do not have Lynch Syndrome.

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How is testing for Lynch syndrome done?

The first step in testing for Lynch syndrome is usually to study tumor tissue from someone in the family who has had colorectal cancer or endometrial cancer. A sample of the tumor is taken from the hospital where the surgery or biopsy took place. By studying this tissue, we can better predict whether additional testing should be done. If this testing shows features of Lynch syndrome, then genetic testing for mutations in the Lynch syndrome genes can be done on a sample of the person’s blood. If a mutation is found, this confirms that the person has Lynch syndrome and other people in the family could be at risk to carry the same mutation.

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What does a negative Lynch syndrome test result mean?

A negative test result means that no mutation was found in any of the Lynch syndrome genes. This can happen if:

  • You have a mutation in one of the Lynch syndrome genes that cannot be detected with the method that was used. No one gene testing method can find all mutations in a gene. 
  • You have a mutation in a different gene. For example, even if you tested negative for Lynch syndrome gene mutations, your genetic counselor may recommend testing for mutations in a different gene that could cause colorectal or other cancers associated with a cancer genetic syndrome. Tests for rare mutations or for panels of multiple predisposition genes are available and may be covered by insurance in some cases. We suggest you talk with your genetic counselor about this. In addition, more genes will probably be discovered in the future.
  • Your personal or family history of cancer happened by chance. For instance, colon cancer is a common cancer. It can develop in several people in the same family without being caused by a genetic mutation.
  • There is a genetic mutation in your family, but you did not inherit it. 
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What does a positive Lynch syndrome test result mean?

People with a mutation in one of the Lynch syndrome genes have Lynch syndrome and are at an increased risk of developing the associated cancers. People with Lynch syndrome have up to an 82% lifetime risk of developing colorectal cancer. Women with Lynch syndrome have up to a 60% lifetime risk of developing endometrial cancer and up to a 15% risk of developing ovarian cancer.

It is important to understand that having Lynch syndrome does not mean that you will definitely develop cancer; it means they you have an increased risk of developing certain cancers. Some people with a Lynch syndrome mutation never develop cancer.

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What does a “variant of uncertain significance” (or “ambiguous”) test result mean?

Genes are written in chemical “letters” called bases. A wrong spelling of a gene can cause an increased risk of cancer. However, changes in the spelling of gene bases may differ in people without cancer. We are still learning which spellings are normal (harmless) and which can cause an increased risk for disease. These kinds of uncertain changes are called “variants of uncertain significance.”

If you have a variant of uncertain significance, we may not be able to tell you whether you are at increased risk for cancer. We will make cancer screening recommendations for you based on your family history. We may suggest testing certain relatives to learn more about the variant, but this information will probably not be helpful in predicting cancer risks for your relatives. Future research may clarify whether a variant of uncertain significance leads to increased risks of cancer.

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How should people with a Lynch syndrome mutation manage their risks of cancer?

People with Lynch syndrome mutations have several options for managing their cancer risks. They can choose to undergo additional cancer screening that is not usually available to people at population risk for cancer. The goal of screening is to try to detect cancer at an early stage if it develops. This includes:

  • Yearly colonoscopy starting at age 20 to 25. Colorectal cancer usually starts as a benign, “pre-cancerous” polyp. 
  • Upper endoscopy is recommended every 2 to 4 years beginning at ages 30 to 35 years. If Helicobacter pylori infection is detected, treatment should be received. If polyposis is diagnosed, upper endoscopy should be repeated more frequently, at an interval to be determined in consultation with a gastroenterologist experienced in the management of the condition.
  • There is no clear evidence to suggest that urinary tract cancer screening with currently available methods will result in a decrease in urinary tract cancer mortality. Members of this family may undergo annual urinalysis or urine cytology beginning at ages 30 to 35 years.

Additional screening guidelines for females with Lynch syndrome include: 

  • Women in this family who may be at risk for Lynch syndrome-associated cancers (endometrial/uterine and ovarian) should consider screening for endometrial cancer with endometrial biopsies every 1 to 2 years starting at age 30 to 35 years. Further evaluation is also recommended for women who may have a change in their normal bleeding pattern. It should be noted that screening has not been show to reduce gynecologic cancer mortality in women with Lynch syndrome and women at significant risk should discuss risk-reducing hysterectomy and bilateral salpingo-oophorectomy (sal-pin-gō ō-fa-rek-ta-mē) with their doctor once child bearing is complete.

It is important to realize that screening does not prevent cancer. Current tests cannot always find cancers when they are small enough to be treated successfully.

Females with Lynch syndrome mutations may choose to undergo surgery to try to prevent cancer. Surgery to reduce the risk of endometrial and ovarian cancer is called a prophylactic or preventive hysterectomy and salpingo-oophorectomy. In rare cases, a cancer of the peritoneum (the lining of the abdomen) can occur after surgery because it is made up of similar tissue as the ovaries, but cannot be removed surgically. There is no proven way to screen for cancer of the peritoneum.

Some medications may decrease the risk of developing cancer. Oral contraceptives may reduce the risk of developing ovarian cancer. In a recent large trial, Lynch syndrome patients who took a high dose of aspirin on a daily basis for several years lowered their risk for colorectal and possibly other Lynch syndrome-associated cancers. While these results are promising, there is not yet enough evidence to make a recommendation for the standard use of aspirin, which can have serious side effects in some people.

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If I have a Lynch syndrome gene mutation, what are the risks to my children?

If you carry a Lynch syndrome gene mutation, each of your children (or future children) has a 50% (1 in 2) chance of inheriting that mutation. A child who inherits the mutation will also inherit the associated cancer risks. It is important to remember that just inheriting the mutation does not automatically mean that a person will develop cancer.

If two individuals with a Lynch Syndrome gene mutation have a child together, there is a 25% (1 in 4) chance that their child will inherit both mutations. Children with mutations in both copies develop the Constitutional Mismatch Repair Deficiency (CMMR-D) Syndrome. People with Lynch Syndrome who have partners at risk for Lynch Syndrome should meet with a reproductive genetic counselor before having children.

Some people with mutations want to know when their children should be tested. The screening for people with Lynch syndrome typically begins in their 20s. Therefore, we do not recommend testing until age 20.

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If I have a Lynch syndrome gene mutation, what are my options for having children?

If a Lynch syndrome gene mutation is identified in your family, you may want to learn about options for family planning (starting a family or having more children). For example, embryos can be tested for the family’s genetic mutation before they are even implanted in a woman’s uterus. This process is called preimplantation genetic diagnosis (PGD). PGD is performed with in vitro fertilization, and may be an option for families who wish to have children without the hereditary cancer risk. To learn more, ask for a PGD-IVF specialist before attempting pregnancy.

Other family planning options include having children with the assistance of donor eggs or sperm or through adoption.

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Who should I call if I have questions?

If you have any questions or concerns, please contact MSK’s Clinical Genetics Service at 646-888-4050.

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