What is Lynch syndrome?

Lynch syndrome is an inherited condition that causes an increased risk for colorectal cancer and cancer in certain other organs.

How common is Lynch syndrome?

Lynch syndrome occurs in approximately 1 in 400 individuals.

What causes Lynch syndrome?

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.

Is Lynch syndrome the same as hereditary non-polyposis colorectal cancer (HNPCC)?

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:

  • At least three relatives have colorectal or other HNPCC-related cancers, with one person being a first-degree relative (parent, child, or sibling) of the other two;
  • At least two generations have been affected;
  • At least one person received a diagnosis of colorectal cancer before age 50;
  • Familial adenomatous polyposis has been excluded.

What are the cancer risks associated with Lynch syndrome?

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%)

  • Lynch syndrome lifetime risk of cancer
    • MLH1/MSH2 Woman, 22 to 53%; Average age at diagnosis: 27 to 46
    • MLH1/MSH2 Man, 27 to 74%
    • MSH6 Woman, 10 to 18%; Average age at diagnosis: 54 to 63
    • MSH6 Man, 18 to 22%
    • PMS2 Woman, 15%; Average age at diagnosis: 47 to 66
    • PMS2 Man, 20%

Cancer type: Endometrial cancer (women only, general population risk is 2.7%

  • Lynch syndrome lifetime risk of cancer
    • MLH1/MSH2 , 14 to 54%; Average age at diagnosis: 48 to 62
    • MSH6, 17 to 71%; Average age at diagnosis: 54 to 57
    • PMS2, 15%; Average age at diagnosis: 49

Cancer type: Stomach cancer (general population risk is <1%)

  • Lynch syndrome lifetime risk of cancer: 0.2 to 13%
  • Average age at diagnosis: 49 to 55

Cancer type: Ovarian cancer (general population risk is ~1.5%)

  • Lynch syndrome lifetime risk of cancer: 4 to 20%
  • Average age at diagnosis: 43 to 45

Cancer type: Hepatobiliary tract cancer (general population risk is <1%)

  • Lynch syndrome lifetime risk of cancer: 0.02 to 4%
  • Average age at diagnosis: 54 to 57

Cancer type: Urinary tract cancer (general population risk is <1%)

  • Lynch syndrome lifetime risk of cancer: 0.2 to 25%
  • Average age at diagnosis: 52 to 60

Cancer type: Small bowel cancer (general population risk is <1%)

  • Lynch syndrome lifetime risk of cancer: 0.4 to 12%
  • Average age at diagnosis: 46 to 49

Cancer type: Brain/central nervous system cancer (general population risk is <1%)

  • Lynch syndrome lifetime risk of cancer: 1 to 4%
  • Average age at diagnosis: 50

Cancer type: Skin cancer (sebaceous carcinoma, keratoacanthomas, sebaceous adenomas)

  • Lynch syndrome lifetime risk of cancer: 1 to 9%
  • Average age at diagnosis: Unknown

Cancer type: Pancreas cancer (general population risk is ~1.5%)

  • Lynch syndrome lifetime risk of cancer: 0.4 to 4%
  • Average age at diagnosis: 63 to 65

Cancer type: Prostate cancer* (general population risk is ~16%)

  • Lynch syndrome lifetime risk of cancer: 9 to 30%
  • Average age at diagnosis: 59 to 60

Cancer type: Breast cancer* (general population risk is ~12%)

  • Lynch syndrome lifetime risk of cancer: 5 to 18%
  • Average age at diagnosis: 52

*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).

Are there other colon risks associated with Lynch syndrome?

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.

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