Lynch Syndrome: Genetic Disorder Raises Risk of Many Cancers

Lynch syndrome is a genetic disorder that increases the risk of developing some types of cancer at a younger age. Most often associated with colorectal cancer and uterine cancer, the disorder affects roughly 1 in 300 people.

Common Cancer Types

Lynch syndrome is caused by mutations in one of four genes: MLH1, MSH2, MSH6 and PMS2. A person’s cancer risk varies depending on which gene mutation is present. Not everyone with Lynch syndrome will develop cancer. But the risk is substantial because of a gene mutation that prevents cells from repairing damage.

Cancers associated with Lynch syndrome include:

• Colorectal
• Endometrial (uterine)
• Ovarian
• Stomach (gastric)
• Small intestine
• Urinary tract (kidney, ureter, bladder)
• Biliary tract (liver, gall bladder, bile ducts)
• Pancreatic
• Prostate
• Brain
• Certain skin cancers

The Importance of Genetic Testing

A family history of Lynch syndrome-associated cancers is an important reason to get genetic testing for the disorder. If one parent has the genes, there’s a 50-percent chance that a child will inherit Lynch syndrome. Children should be screened for this condition because this risk is very high.

Genetic testing is also recommended for anyone who has had colorectal or uterine cancer before age 50, or who has had more than one Lynch syndrome-associated cancer. In addition, genetic testing is recommended when a patient’s tumor has certain features that are consistent with Lynch syndrome.

Cancer Prevention & Screening

People with Lynch syndrome are urged to undergo preventive cancer screenings at an earlier age than usual. Screening recommendations vary according to the results of genetic testing. Providers may have specific screening recommendations based on their patient’s personal and family health history. However, general screening guidelines for people with Lynch syndrome include the following:

• Colorectal Cancer:
  • People with MLH1 or MSH2 or EPCAM Lynch syndrome should begin getting colonoscopies at age 20 to 25, or two to five years earlier than the youngest age at which colorectal cancer was diagnosed in their family. Colonoscopies should be repeated every one to two years.
  • People with MSH6 or PMS2 Lynch syndrome should begin getting colonoscopies at ages 30 to 35, or two to five years earlier than the earliest age of colorectal cancer diagnosed in their family, if that age is under 30. Colonoscopies should be repeated every one to three years.
• Stomach and Small Bowel Cancer: Screening with an upper endoscopy can start between ages 30 to 40 and should be repeated every two to four years. Earlier testing may be done if you have a family history of upper digestive cancers or high-risk factors, such as Barrett's esophagus or stomach polyps.
• Gynecological Cancer (Endometrial or Uterine): Women with Lynch syndrome are advised to consider having an endometrial biopsy every one or two years starting at ages 30 to 35 to be considered for risk-reducing surgery.
• Ovarian Cancer: Preventive surgeries, such as hysterectomy or oophorectomy, can help reduce the chances of a woman with Lynch syndrome developing ovarian cancer.
• Pancreatic Cancer: Pancreatic cancer screening for people with Lynch syndrome usually begins at age 50 or 10 years earlier than the youngest age of a pancreatic cancer diagnosis in the family.
• Skin Cancer: A skin exam is recommended every one to two years for people with Lynch syndrome. Your healthcare provider can decide when to begin skin cancer screenings.
• Prostate Cancer: For men with Lynch syndrome, annual prostate-specific antigen testing is recommended beginning at age 40, with testing to continue every other year.
• Breast Cancer: To date, research hasn't established a clear link between Lynch syndrome and an increased risk of breast cancer. However, some data indicates that women with MSH6 or PMS2 mutations may have a slightly elevated risk. For now, women with Lynch syndrome should follow standard guidelines for breast cancer screening based on their individual and family history.

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At University Hospitals Seidman Cancer Center, our care team provides the most advanced forms of cancer care, from prevention, screening, diagnosis, treatment through survivorship.