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Lynch Syndrome

What is Lynch syndrome?

Lynch syndrome is a hereditary condition that makes a person more likely to develop cancer. Other names for Lynch syndrome include Hereditary Nonpolyposis Colorectal Cancer syndrome (HNPCC) and Muir-Torre syndrome. Colorectal cancer and uterine (endometrial) cancer are the two cancers a person with Lynch syndrome is at greatest risk to develop; however, these risks and other cancer risks may be reduced through specialized medical care.

Lynch syndrome is one of the most common causes of hereditary cancer risk with approximately one in 270 people affected. Lynch syndrome causes about three to five percent of colon cancers and two to three percent of uterine cancers.

It is important to note that not every person with Lynch syndrome develops cancer, but the odds of developing cancer are much greater than average. Fortunately, interventions are available to carefully monitor for cancer, as well as to reduce cancer risk. Within Penn Medicine's Gastrointestinal Cancer Genetics Program, the Lynch Syndrome Management Program has been specifically designed to help provide state-of-the-art, compassionate care and proactive health management for individuals and families with Lynch syndrome.

Lynch Syndrome Management

An important way to decrease cancer risk in Lynch syndrome is through performing appropriate screening and implementation of risk-reduction strategies, such as colonoscopy.

With Penn Medicine's Lynch Syndrome Management Program, you will meet with a physician with expertise in Lynch syndrome on a yearly basis to review your personal medical history, genetic testing results, and family medical history in order to provide an individualized, comprehensive Lynch syndrome management plan. This plan will cover recommendations for cancer screening and/or risk reduction options, addressing risks for Lynch syndrome-associated cancers, including: gastrointestinal tract cancer (colorectal, gastric, small intestinal, pancreatic), gynecologic cancer (uterine and ovarian, if applicable), urinary tract cancer and skin cancer among others. The Lynch Syndrome Management Plan will also cover important topics, such as: chemoprevention (taking medications to decrease cancer risk), family planning, and genetic testing of potentially at-risk relatives.

Patients seen in the Lynch Syndrome Management Program will meet with either Bryson Katona, MD, PhD, Director of Penn Medicine's Gastrointestinal Cancer Genetics Program, or Kirk Wangensteen, MD, PhD.

Lynch Syndrome FAQs

Below you'll find the answers to frequently asked questions about Lynch syndrome, cancer risk and genetic testing.

What causes Lynch syndrome?

Genes are instructions for how the body grows and functions. Our genes are inherited (passed down) from our parents. Some genes help determine traits like hair color or eye color. Other genes may increase or decrease the chance of disease, such as developing cancer.

A person with Lynch syndrome is born with a mutation (harmful genetic change) in one of the following genes: MLH1, MSH2, MSH6, PMS2 or EPCAM. Typically, these genes help the body prevent cancer from developing. When a mutation is present, the gene is unable to perform its normal role in cancer prevention, thus causing a person with Lynch syndrome to have a greater chance for cancer to develop.

How do mutations in Lynch syndrome genes increase cancer risk?

The genes that are responsible for causing Lynch syndrome are involved in the DNA mismatch repair system. This system is very important for cells to repair errors that inevitably occur in DNA over a person’s lifetime. Repairing errors in DNA is important to maintaining the integrity of DNA, as errors that occur in certain places in the DNA can lead to the development of cancer.

What are the cancer risks related to Lynch syndrome?

There are two types of cancers most likely to develop in a person with Lynch syndrome: colon cancer and, for women, uterine (endometrial) cancer. Other cancers for which individuals with Lynch syndrome may have increased risk (to a lesser degree) include: stomach (gastric), ovarian, small intestinal, hepatobiliary (liver and bile duct), pancreatic, and urinary tract, as well as sebaceous skin cancers.

The magnitude of the cancer risks in Lynch syndrome depend in part on the gene that is mutated (see chart below for gene specific risks). Families with a mutation in the MLH1 gene or MSH2 gene (and possibly also the EPCAM gene) are considered to have higher cancer risks, whereas families with a mutation in the MSH6 gene or PMS2 gene are considered to have lower risks for cancer (but still higher cancer risk than a person without Lynch syndrome). It is important to note that not every person with a Lynch syndrome gene mutation develops cancer, but the odds of developing cancer are much greater than average.

Lifetime cancer risks (specifically colorectal and uterine) associated with mutations in Lynch syndrome genes are shown below. There are other cancer risks that are not included in the chart below. It is also important to remember some of these risks may be reduced through specialized medical care.

Cancer Site Colorectal Cancer Endometrial (Uterine) Cancer
General population risk 4.2% 3.1%
MLH1 46-61% 34-54%
MSH2 & EPCAM 33-52% 21-57%
MSH6 10-44% 16-49%
PMS2 9-20% 13-26%
Cancer Site General Population Risk MLH1 Lynch Syndrome Risk
Colorectal Cancer 4.5% 46-49%
Endometrial Cancer 2.7% 43-57%
Gastric Cancer <1% 5-7%
Ovarian Cancer 1.3% 5-20%
Small Intestinal Cancer <1% Up to 11%
Pancreas Cancer 1.5% 6%
Bladder Cancer 2.5% 2-4%
Urothelial Cancer <1% Up to 5%
Biliary Tract Cancer <1% 2-4%

How is Lynch syndrome inherited?

All of our genes are present in pairs. One copy in each pair is from our mother, and the other copy is from our father. Inheriting a single mutation in one copy of any of the Lynch syndrome genes causes Lynch syndrome. This is called dominant inheritance.

A person with a Lynch syndrome gene mutation has a 50 percent chance of passing the gene mutation to a child. Men and women are equally at risk of inheriting a gene mutation causing Lynch syndrome. If a child does not inherit the gene mutation, the mutations cannot be passed along to the next generation by this child as these gene mutations do not skip a generation.

When should genetic testing for Lynch syndrome be considered?

Families with Lynch syndrome may have several relatives in multiple generations affected by a Lynch syndrome cancer. The cancers seen in Lynch syndrome also may arise at earlier than average ages.

In general, genetic testing for Lynch syndrome may be appropriate for a person with the following:

  • Colon cancer or uterine cancer before age 50
  • A history of more than one Lynch syndrome-associated cancer (i.e., colon cancer plus uterine cancer)
  • Multiple family members with Lynch syndrome-associated cancers
  • A family member with a known diagnosis of Lynch syndrome
  • A tumor with features suggestive of Lynch syndrome (i.e., tumor testing by a Pathologist may show an abnormal result on mismatch repair immunohistochemistry, also known as an MMR-IHC test)

How can an individual with Lynch syndrome manage cancer risk?

Given the multiple increased cancer risks in Lynch syndrome, it is important that individuals with Lynch syndrome be managed by a multi-disciplinary team of providers with expertise in Lynch syndrome.

What are some Lynch syndrome patient resources?

If you or a family member has Lynch syndrome, we recommend the following resources:

Lynch Syndrome Research Opportunities

Through the Gastrointestinal Cancer Genetics Program at Penn Medicine, there are multiple research opportunities, for which individuals with Lynch syndrome may be eligible to participate. Research is critical to better understanding cancer risks and cancer prevention in Lynch syndrome, which is important for moving the Lynch syndrome field forward to improve the lives of patients and families affected by this condition.