Peutz-Jeghers Syndrome

This content has been reviewed and approved by

William J. Gradishar, MD FACP
Director, Breast Medical Oncology, Professor of Medicine
Robert H. Lurie Comprehensive Cancer Center
Northwestern University Feinberg School of Medicine

The risk for breast and ovarian cancer is increased with Peutz-Jeghers syndrome (PJS). This is a rare inherited disorder. It is associated with specific physical characteristics in addition to increased cancer risks. The features associated with Peutz-Jeghers syndrome may include the following: 

• Melanocytic macules (dark blue or brown moles). These moles may be located around and/or in the mouth (including the lips), and around the eyes, nostrils, and anus. Dark moles may also appear on the fingers. The moles may fade by adulthood
• Multiple polyps in the gastrointestinal tract 
• Increased risk of benign (noncancerous) tumors of the ovaries and testes
• Increased risk of stomach, esophageal, breast, colon, pancreatic, and ovarian cancers

What causes Peutz-Jeghers syndrome?

Peutz-Jeghers syndrome is caused by mutations in a gene on chromosome 19. That gene is known as STK11. Mutations in this gene are identified in about 70 percent of familial cases. Peutz-Jeghers syndrome is associated with up to a 93 percent chance of developing one of the associated cancers by age 64. The risks of breast and ovarian cancer are similar to those from mutations in the BRCA1 and BRCA2 genes.

The STK11 gene is a tumor suppressor gene. It usually controls cell growth and cell death. Both copies of a tumor suppressor gene must be altered (mutated) before a person will develop cancer. With Peutz-Jeghers syndrome, the first mutation is inherited from either the mother or the father. It is therefore present in all cells of the body. This is called a germline mutation.

Whether a person who has a germline mutation gets cancer and where the cancer develops depend on where (in which cell type) the second mutation occurs. For example, if the second mutation is in the breast, then breast cancer may develop. If it is in the colon, then colon cancer may develop. But other mutations are needed also to lead to cancer.

Mutation of both copies of STK11 is just the first step in the process. What causes these additional mutations is unknown. Possible causes include chemical, physical, or biologic agents in the environment or chance errors that happen when cells reproduce.

Some people who have inherited a germline STK11 mutation never develop cancer because they never get the second mutation. This can make the cancer appear to skip generations in a family, when in reality the mutation is present. People with a mutation, regardless of whether they develop cancer, have a 50-50 chance of passing it on to their children.

The STK11 gene is not located on the sex chromosomes. This means that mutations can be inherited from the mother's or the father's side of the family.