Women's Health Issues : Breast Health : About Breast Cancer : Women's health : Breast Cancer Genetics
The risk for breast and ovarian cancer is increased with Peutz-Jeghers syndrome (PJS), a rare early-onset autosomal dominant disorder. It's associated with specific physical characteristics in addition to increased cancer risks. The features associated with PJS may include the following:
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. These lesions 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, cervical, and ovarian cancers
Peutz-Jeghers syndrome is caused by mutations in a gene on chromosome 19 known as STK11. Genetic testing is available. A positive family history is found in about half of the people who are diagnosed with PJS. The other half have no previous family history. Almost all people with PJS will be diagnosed with one or more of the associated cancers during their lifetime.
The STK11 gene is a tumor suppressor gene. This gene usually controls cell growth and cell death. Both copies of a tumor suppressor gene must be altered, or mutated, before a person will develop cancer. With PJS, the first mutation is inherited from either the mother or the father and is present from birth in all cells of the body. This is called a germline mutation. Whether a person who has a germline mutation will develop cancer and where the cancer(s) will develop depends on where (which cell type) the second mutation happens. 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. The process of tumor development actually needs mutations in multiple growth control genes. Loss 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 biological environmental exposures or chance errors in cell replication.
Some people who have inherited a germline STK11 mutation never develop cancer. This is because they never get the second mutation necessary to knock out the function of the gene and to start the process of tumor formation. 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 to pass the mutation on to each of their children.
It is also important to remember that the STK11 gene is not located on the sex chromosomes. Therefore, mutations can be inherited from the mother's side or the father's side of the family.