Causes of Peutz-Jeghers Syndrome
Peutz-Jeghers syndrome is caused by mutations in a gene on
chromosome 19 known as STK11. Mutations in STK11 are identified in
about 70% of familial cases. Peutz-Jeghers syndrome is associated with
up to a 93% chance of developing one of the associated cancers by age
64. The risks of breast and ovarian cancer fall within the ranges
associated with mutations in the BRCA1 and BRCA2 genes.
The STK11 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
Peutz-Jeghers 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 breast, then
breast cancer may develop. If it is in the colon, then colon cancer
may develop. The process of tumor development actually requires
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 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 STK11 mutation never
develop cancer 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. 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 STK11 gene is not located
on the sex chromosomes. Therefore, mutations can be inherited from the
mother or the father's side of the family.