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Cowden syndrome is caused by mutations in a gene on chromosome 10 known as PTEN. About 80% of people whose symptoms meet the criteria for a diagnosis of Cowden syndrome will have a PTEN mutation. Mutations in PTEN confer a 25-50% lifetime risk for breast cancer, about a 10% risk of thyroid cancer, and potentially up to a 5-10% risk of endometrial cancer, although this risk is still being evaluated.
The PTEN gene is a tumor suppressor gene, which 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 Cowden syndrome, the first mutation is inherited from either the mother or the father and is therefore present 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 upon where (which cell type) the second mutation occurs. For example, if the second mutation is in the thyroid, then thyroid cancer may develop. If it is in the breast, breast cancer may develop. The process of tumor development actually requires mutations in multiple growth control genes. Loss of both copies of PTEN is just the first step in the process. What causes these additional mutations to be acquired is unknown. Possible causes include chemical, physical, or biological environmental exposures or chance errors in cell replication.
Some individuals who have inherited a germline PTEN mutation never develop cancer because they never get the second mutation necessary to knock out the function of the gene and 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. Persons with a mutation, regardless of whether they develop cancer, however, have a 50/50 chance to pass the mutation on to the next generation.
It is also important to remember that the PTEN gene is not located on the sex chromosomes. Therefore, mutations can be inherited from the mother or the father's side of the family.