Lynch syndrome occurs in approximately 1 in 400 individuals.
Lynch syndrome is caused by a mutation (genetic change) in one of five specific genes that are responsible for fixing errors in DNA. To further explain, DNA are the codes that carry genetic information. Every time cells divide, the DNA duplicates. Sometimes errors occur during DNA duplication that damages cells and affects the way cells grow. A buildup of these damaged cells may lead to cancer. Usually, a gene called the DNA mismatch repair (MMR) gene finds and fixes the errors before they damage the cell. People with Lynch syndrome have a mutation in the MMR gene, which means the errors are less likely to be found and fixed, which increases the risk of developing certain cancers.
Sometimes Lynch syndrome is also referred to as hereditary non-polyposis colorectal cancer (HNPCC), but the two conditions are subtly different.
Lynch syndrome is classified by a mutation in the MMR gene. HNPCC is defined by family history and individuals must meet specific criteria, which are:
The specific organs at risk for cancer and the degree of increased risk depends on the gene that mutated and, in some cases, if the patient is male or female. The specific genes associated with Lynch syndrome are MLH1, MSH2, MSH6, PMS2, and EPCAM. The list below shows the organs at risk, lifetime risk of developing cancer and average age that cancer is diagnosed.
Cancer type: Colorectal cancer (general population risk is ~5%)
Cancer type: Endometrial cancer (women only, general population risk is 2.7%
Cancer type: Stomach cancer (general population risk is <1%)
Cancer type: Ovarian cancer (general population risk is ~1.5%)
Cancer type: Hepatobiliary tract cancer (general population risk is <1%)
Cancer type: Urinary tract cancer (general population risk is <1%)
Cancer type: Small bowel cancer (general population risk is <1%)
Cancer type: Brain/central nervous system cancer (general population risk is <1%)
Cancer type: Skin cancer (sebaceous carcinoma, keratoacanthomas, sebaceous adenomas)
Cancer type: Pancreas cancer (general population risk is ~1.5%)
Cancer type: Prostate cancer* (general population risk is ~16%)
Cancer type: Breast cancer* (general population risk is ~12%)
*Experts are still unsure whether breast and prostate cancer are part of Lynch Syndrome or not.
The colon cancers caused by Lynch syndrome tend to be more common on the right side of colon and develop much more quickly than in the general population (1 to 2 years versus 10 years). In addition, patients who have a colorectal cancer have a significantly increased risk of developing a second colorectal cancer. This risk is approximately 15 percent within 10 years after the original surgery, 40 percent within 20 years, and 60 percent after 30 years, depending on which surgery is performed.
Some individuals with Lynch syndrome will have a form of the condition called Muir-Torre syndrome. Individuals with Muir-Torre syndrome are prone to develop the cancers listed above as well as benign skin growths (sebaceous adenomas, keratoacanthomas) and skin cancers (sebaceous carcinoma).
Individuals with Lynch syndrome may develop a few colorectal polyps, called adenomas, in the colon or rectum. If these polyps are not detected and removed, they could develop into a cancer. Having regular screening colonscopies is important for detecting and removing these polyps.
Screening tests and genetic testing are used to diagnose Lynch syndrome. A biopsy of the tumor is used for two screening tests. One test looks for changes that indicate the gene that affects DNA repairs is not working. These changes are called microsatellite instability or MSI. Tumors that have microsatellite instability are called MSI-high (MSI-H). Some 90 to 95 percent of colorectal cancers (and many endometrial cancers) from individuals with Lynch syndrome are MSI-H. This means that the cancer in the family is likely due to Lynch syndrome. However, since about 5 to 10 percent of Lynch syndrome tumors do not show instability, a negative MSI-H test cannot completely rule out the possibility of a Lynch syndrome diagnosis.
There is a second type of screening test for Lynch syndrome that uses a technique called immunohistochemistry (IHC). IHC testing is a screening test done on the tumor that looks for the expression of Lynch syndrome gene products (proteins). If one or more of the proteins are missing in the tumor, it suggests that there is a mutation in that gene, which could then be found through genetic testing. Approximately 88 percent of individuals with Lynch syndrome will have an abnormal IHC result.
Ideally, MSI and/or IHC testing should be done before genetic testing is ordered. However, there are occasions where MSI or IHC cannot be done, in which case genetic testing can be performed. Genetic counseling is recommended before ordering genetic testing. Genetic testing, which involves a blood draw or obtaining a brushing from the inside of the mouth (buccal swab), helps determine if a MLH1, MSH2, MSH6, PMS2, or EPCAM gene mutation is present in the family.
If genetic testing reveals a mutation, a diagnosis of Lynch syndrome is confirmed. Other family members can then be tested. Any other family members who have a mutation would also be at an increased risk for developing cancers associated with Lynch syndrome and should be monitored. If no mutation is found, Lynch syndrome is not necessarily excluded. A genetic counselor can further discuss the meaning of negative genetic test results and cancer risk.
Lynch syndrome is an autosomal dominant disorder. This means that if only one parent carries the mutation for Lynch syndrome, there’s a 50 percent chance a child of the parents will inherit the mutation.
Individuals diagnosed with Lynch syndrome should tell their family members and encourage them to undergo genetic counseling. Counseling includes an evaluation of their personal and family history as well as and genetic testing for the Lynch syndrome gene mutation.
Currently, there is no cure for Lynch syndrome.
Lynch syndrome is an inherited condition and cannot be prevented. However, patients with Lynch syndrome should undergo lifelong cancer screening beginning in adulthood. The screening recommendations are:
For colorectal cancers:
For endometrial and ovarian cancers:
For other cancers:
While aspirin has been shown to reduce risk, the exact dosage of aspirin is still being determined. Therefore, we have not made prescribing this part of our routine practice until dosage information is more fully investigated.
It’s highly recommended that individuals diagnosed with Lynch syndrome be managed by clinicians with expertise in treating the condition. Because Lynch syndrome can affect many organ systems, the care team will include a variety of clinicians. Team members may include gastroenterologists, surgeons, gynecologic oncologists, urologists, dermatologists, gynecologists, primary care physicians, geneticists, genetic counselors and oncologists.
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This information is provided by the Cleveland Clinic and is not intended to replace the medical advice of your doctor or healthcare provider. Please consult your healthcare provider for advice about a specific medical condition. This document was last reviewed on: 09/05/2018