Peutz-Jeghers syndrome

What Does It Mean to Test Positive for an STK11 Mutation?

Mutations in STK11 are associated with a condition known as Peutz-Jeghers syndrome (PJS). PJS is an inherited condition that has distinct physical characteristics, including specific skin freckling, often on the lips and mouth; and the growth of polyps in the intestinal tract.

Most often, those who are determined to be affected with PJS can be diagnosed based on their physical characteristics and family history. Individuals with an STK11 mutation also have an increased risk for a variety of cancers, both in the digestive system and in other organs, compared to that of the general population.

What Are the Cancer Risks Associated with an STK11 Mutation?

Men and women have up to a 39% lifetime risk for cancer impacting the digestive system. Women also have up to a 50% lifetime risk for breast cancer and an increased risk for gynecological cancers (ovarian and uterine). The following table outlines specific cancer risks further:

Cancer Type Risk General Population's Risk
Breast Cancer (Women Only) 45-50% 12.4%
Colon Cancer 39% 4.5%
Pancreatic Cancer 11-36% 1.6%
Gastric (Stomach) Cancer 29% <1%
Ovarian Cancer (Women Only) 18-21% 1.3%
Small Intestine 13% <1%
Cervical Cancer 10% <1%
Endometrial (Uterine) Cancer 9% 2.8%
Testicular Cancer 9% <1%
Lung Cancer 15-17% 6.4%

STK11 mutation carriers are encouraged to work with a multidisciplinary care team to manage the risks described above.

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

The most important aspect of management of an individual with an STK11 mutation is increased cancer screening, to allow the earliest possible detection of any tumors.

For Women

  • Beginning at age 18, women should be familiar with their breasts and promptly report any changes to a healthcare provider.
  • Beginning at age 25, clinical breast examinations are recommended every six months.
  • Beginning at age 25 or earlier, based on the earliest age of breast-cancer diagnosis in the family, breast imaging with MRI and/or mammograms are recommended.
    • For women ages 25 to 29, annual breast MRIs are the preferred screening method.
    • For women ages 30 to 75, annual MRI and mammogram with consideration of 3D mammogram (tomosynthesis) are recommended.
    • For women over the age of 75, breast-cancer screening can be considered on an individual basis.
  • Beginning at age 18, annual pelvic examinations and pap smears are recommended. Transvaginal ultrasound (a special type of ultrasound inserted into the vagina to view the genital tract and ovaries) can also be considered.
  • Additional risk-reduction strategies, such as prophylactic mastectomy (surgical removal of both breasts) or the use of preventative medication, may also be considered on an individualized basis. These strategies, however, are not routinely recommended at this time.

For Men

  • Annual physical examinations, including testicular examinations, are recommended (ideally beginning by age 10).

For Men and Women

  • Colonoscopies are recommended beginning in the late teens. The frequency of follow-up colonoscopy is determined based on findings from the initial evaluation. By age 18, colonoscopy is generally repeated every two to three years.
  • Upper endoscopy is recommended beginning in the late teens, to be repeated every two to three years.
  • Imaging of the small intestine via CT, MRI, or capsule endoscopy is recommended beginning between ages 8 to 10. After age 18, this screening is generally repeated every two to three years.
  • Imaging of the pancreas by MRI and/or endoscopy every one to two years is recommended beginning at ages 30 to 35.

No specific screening recommendations have been made for management of lung-cancer risk associated with STK11 mutations, but mutation carriers are encouraged to avoid tobacco use.

What Is the Chance That Family Members of STK11 Mutation Carriers Have the Same Mutation?

STK11 mutations are passed down in a family. This means that family members of STK11 mutation carriers may have the same mutation and may also have an increased risk of developing cancer. For this reason, it is important for STK11 mutation carriers to discuss genetic test results with family members.

  • Close blood relatives of STK11 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 STK11 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 found on one side of the family, and it is more likely to be inherited from the side of the family that has a strong history of cancer.

Genetic testing of family members can help determine which family members may have an increased risk for cancer and may benefit from the screening and/or risk-reduction options discussed above. Family members who test negative for a known familial STK11 mutation likely have the same risk for cancer as the general population and can follow the general population's screening guidelines.

What Else Should STK11 Mutation Carriers Know?

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.