MSH2-associated Lynch syndrome

What Does It Mean to Test Positive for an MSH2 Mutation?

Mutations in MSH2 are associated with Lynch syndrome. Individuals with an MSH2 mutation are at increased risk of developing certain cancers, with the greatest risk being for colon cancer. Women also have an increased risk of uterine (endometrial) and ovarian cancers. However, it is important to understand that the risk for cancer is not 100%, which means that not everybody with an MSH2 mutation will develop cancer.

What Are the Cancer Risks Associated with an MSH2 Mutation?

MSH2 mutations are primarily associated with an increased risk of colon cancer in both men and women. Other cancers involving the stomach, hepatobiliary tract, small intestine, urinary tract, brain, pancreas, and skin are also associated. Women are known to have an increased risk of uterine (endometrial) cancers and ovarian cancer.

In most cases, the risk for cancer is reported as a range. Precise risk estimates are not available at this time because further research is needed to investigate how environmental or other genetic factors play a role in the development of cancer among individuals with MSH2 mutations.

Cancer Risks and Average Age of Onset

For individuals who have never had a cancer diagnosis, the lifetime risk of developing a Lynch-syndrome-related cancer is substantially increased compared to that of the general population.

For individuals who have never had colon cancer, the risk of developing colon cancer may be as high as 82% compared to the general population's risk of approximately 4%. For women, the lifetime risk of developing a cancer of the uterus or ovaries may be as high as 60% and 24% respectively, compared to the general population's risk of less than 3%.

The following table details the different cancers associated with MSH2 mutations and the average age when a cancer diagnosis generally occurs:

Cancer Type Cancer Risk Average Age of Onset General Population Risk
Colon 52 to 82% 44 to 61 Years 4.3%
Uterine (Endometrial)* 25 to 60% 48 to 62 Years 2.8%
Stomach 6 to 13% 56 Years < 1%
Ovarian* 15 to 24% 43 Years 1.3%
Liver/Gallbladder 1 to 4% 50 to 57 Years 1%
Intestinal (Small Bowel) 3 to 6% 47 to 49 Years < 1%
Brain/CNS 1 to 3% 50 Years < 1%
Sebaceous Neoplasm (Skin) 1 to 9% Unknown < 1%
Pancreas 1 to 6% Unknown 1.6%

*Uterine and ovarian cancers only affect females.

What Cancer-Screening or Risk-Reducing Options Are Available?

There are several options available to individuals found to have an MSH2 mutation, including more-frequent and more-specialized screenings. For women, the additional option of risk-reducing surgery is also available.

Cigarette smoking has been associated with an increased risk of colon cancer in individuals with an MSH2 mutation. Therefore, mutation carriers are encouraged to avoid tobacco products.

Aspirin may decrease the risk of colon cancer in individuals with an MSH2 mutation, but more studies must be done to understand the optimal dose and duration of treatment.

Cancer Screening

The most important aspect of management of an individual with an MSH2 mutation is increased cancer screening, to allow the earliest detection of any tumors.

  • Colonoscopy is recommended beginning between ages 20 and 25 years or earlier, based on family history. It is recommended to repeat colonoscopy every one to two years.
  • For selected individuals, upper endoscopy beginning between ages 30 and 35 may be recommended. In general, this procedure is completed every three to five years depending on findings. This is reported to be of particular importance to individuals with a positive family history of a stomach or other intestinal cancer and for individuals of Asian descent.
  • Annual analysis of the urine beginning between the ages of 30 and 35 is recommended.
  • Annual physical or neurologic examination starting at 25 to 30 years may be considered.
  • Pancreatic cancer screening guidelines are not as well established, and additional data is needed to determine their effectiveness. However, the Cancer of the Pancreas Screening Consortium (CAPS) recommends that individuals with Lynch syndrome who have a family history of pancreatic cancer in a first-degree relative (e.g., parent, sibling, or child) consider screening beginning at age 50. Screening may include evaluation of biomarkers, MRI of the abdomen, and endoscopy studies.

Additional Considerations for Women

Because an MSH2 mutation is known to increase the risk of endometrial and ovarian cancer, women have the following additional screening and risk-reducing considerations:


  • MSH2 carriers, like all women, should be aware of the signs and symptoms of cancer and the importance of prompt reporting and evaluation of these symptoms. Note: many of these symptoms are normal for healthy women to experience on occasion. Any symptoms lasting for several weeks or any change from a women’s baseline should be discussed promptly with a healthcare provider.
    • Possible signs or symptoms of uterine (endometrial) cancer include abnormal uterine bleeding or postmenopausal bleeding.
    • Possible signs or symptoms of ovarian cancer include pelvic or abdominal pain, bloating, difficulty eating, feeling full quickly, or increased urinary frequency or urgency.
  • Endometrial screening biopsy every one to two years is an option for carriers of MSH2 mutations.
  • Transvaginal ultrasound (a special type of ultrasound inserted into the vagina to view the genital tract and ovaries) and a CA-125 blood test can be considered. However, these procedures have not been shown to be effective strategies for screening in women at high risk for ovarian cancer.

Risk-Reducing Surgery

  • Removal of both ovaries and fallopian tubes (bilateral salpingo-oophorectomy) reduces the risk of ovarian cancer significantly. Removal of the uterus (hysterectomy) is also an option to reduce the risk of endometrial cancer. The timing of a risk-reducing surgery should be individualized based on family history, menopausal status, family planning, and overall health.

What Is the Chance That Family Members of MSH2 Mutation Carriers Have the Same Mutation?

MSH2 mutations are passed down in a family. This means that family members of MSH2 mutation carriers may have the same mutation and may also be at increased risk to develop cancer. For this reason, it is important for MSH2 mutation carriers to discuss genetic test results with family members.

  • Close blood relatives of MSH2 mutation carriers, such as parents, siblings, and children, have a 50% chance of having the same mutation.
  • Distant relatives, such as aunts, uncles, grandparents, and cousins, also have a chance of having the same MSH2 mutation.
  • A physician or a genetic counselor can help mutation carriers determine whether the mutation was more likely to have been inherited from the maternal or paternal side of the family. In general, the mutation will only be inherited from one side of the family, and it is more likely to be inherited from the side of the family that has a history of colon cancer.

Genetic testing of family members can help determine which family members are at increased risk for cancer and may benefit from screening and/or risk-reduction options discussed above. Family members who test negative for a known familial MSH2 mutation likely have the same risk for cancer as that of the general population and can follow the general population's screening guidelines.

What Else Should MSH2 Mutation Carriers Know?

In rare instances, an individual may inherit two mutations in MSH2, one from each parent. This has the potential to result in a rare condition called constitutional mismatch repair deficiency (CMMRD). Individuals with CMMRD have a very high risk of developing cancer and may develop cancer in infancy or childhood. For individuals who test positive for MSH2, it may be appropriate to consider carrier screening for MSH2 mutations in a spouse or partner.

Mutation carriers who are interested in options to prevent passing their mutation to future children may wish to consider preimplantation genetic diagnosis (PGD). PGD is a procedure that involves in vitro fertilization (IVF) and can determine if an embryo carries the genetic mutation present in a family. Determining which embryos carry a family mutation may allow a mutation carrier to prevent the condition from being passed to future children. The decision to undergo PGD is personal. Mutation carriers and their family members can talk with a healthcare provider to learn more about their reproductive options.