What Is Lynch Syndrome?

This blog post was updated on March 21, 2019.

Lynch syndrome is the most common hereditary form of colorectal cancer. In the United States, about 140,000 new cases of colorectal cancer are diagnosed each year and approximately 3 to 5 percent of these cancers are caused by Lynch syndrome.

Individuals with Lynch syndrome have a 50 to 80 percent lifetime risk of developing colorectal cancer compared to 2 percent in the general population. Women with Lynch syndrome also carry a 40-60 percent lifetime risk of developing endometrial cancer.

In addition to higher colorectal and endometrial cancer risk, individuals with Lynch syndrome also carry an increased risk of developing cancers of the stomach, small intestine, pancreas, liver, gallbladder ducts, upper urinary tract, brain, and skin. Women with the syndrome also have a higher risk for ovarian cancer.

Lynch syndrome is a hereditary condition that can increase risk for certain cancers. Meeting with a provider who specializes in Lynch syndrome can help patients understand and manage risk.
Lynch syndrome is a hereditary condition that can increase risk for certain cancers. Meeting with a provider who specializes in Lynch syndrome can help patients understand and manage risk.

What causes Lynch syndrome?

Lynch syndrome is caused by an inherited alteration in one of five genes: MLH1, MSH2, MSH6, PMS2, and EPCAM. The first four of these genes are involved in a process called mismatch repair—they act like spellcheckers to find and correct the “typos” made in the gene copying process. Mutations (harmful changes) in any one of these genes can lead to the accumulation of more and more of these mistakes that happen as a normal part of the DNA replication process and can thus predispose a person to cancer.

Mutations in the fifth gene, EPCAM, are also a cause of Lynch syndrome because of EPCAM’s nearness to the MSH2 gene; certain types of changes in the EPCAM gene can cause the MSH2 gene to shut off. If a person has inherited a mutation in one of these five genes, then they are at risk for developing the cancers seen in Lynch syndrome.

Who is at risk?

If colorectal or endometrial cancer run in your family, it’s possible the gene mutation that causes Lynch syndrome has been passed down.

If you believe you may be at risk, speak with a doctor about potential genetic testing and steps for prevention.

How is Lynch syndrome managed?

Regular screening can help detect early stages of cancer and some preventive measures can lower risk of certain cancers. There are a variety of monitoring and treatment options available:

Colorectal cancer:

  • Regular colonoscopies can effectively screen for the development of colorectal cancer and help diagnose it in its earlier, and more treatable, stages.
  • While it isn’t certain, studies have shown that some people with Lynch syndrome who take high doses of aspirin daily for more than two years may have a reduced risk of Lynch syndrome-associated cancer.

Endometrial cancer:

  • Because the screening for endometrial cancer has not been proven to be very effective at detecting early cancer, women with Lynch syndrome may consider removal of the uterus (and sometimes ovaries) after they have completed their families and are physically and emotionally ready.
  • For those women with Lynch syndrome who are not ready to have preventative surgery, they should keep an eye out for any irregular or unusual vaginal bleeding, as that can indicate the early development of cancer. Oftentimes doctors will offer an annual pelvic ultrasound and endometrial biopsy beginning at 35.
  • Oral contraceptives may also aid in cancer prevention.

Screening for other Lynch syndrome associated cancers include:

  • Annual skin examinations
  • Endoscopy of the upper gastrointestinal tract
  • Annual urine tests

If you or a family member is diagnosed with Lynch syndrome, it’s important to get the appropriate surveillance, tests, and procedures based on your specific circumstances. The clinical team at Dana-Farber’s Lynch Syndrome Center provides ongoing, individualized, comprehensive, and centralized care geared to reducing cancer risk in individuals with Lynch syndrome.