People with a personal or family history of multiple colorectal polyps may be familiar with well-known hereditary syndromes causing colorectal polyposis and cancer. These include Familial Adenomatous Polyposis (FAP) and MYH Associated Polyposis (MAP). Recently, another syndrome was added to the genetics alphabet soup – Polymerase Proofreading Associated Polyposis, or PPAP for short.
PPAP is caused by mutations in the POLD1 and POLE genes. Although exact cancer risks are yet to be determined, anyone with PPAP has an increased risk for colorectal polyps and/or cancer. There may also be an increased risk for extracolonic (outside the colon) tumors including endometrial cancer and brain tumors.
Early data suggest that POLD1 mutations are more often associated with a Lynch syndrome-like phenotype (colorectal cancer and extracolonic tumors) whereas POLE mutations are more often associated with a polyposis phenotype (multiple colorectal polyps). Additional studies are needed to confirm these associations and clarify cancer risks.
Because a limited number of individuals are currently known to have PPAP, standard medical management guidelines have not yet been created. Proposed guidelines are typically based on well-established recommendations for individuals with FAP and Lynch syndrome due to the overlapping clinical features of these conditions. As always, medical management guidelines should also be personalized according to an individual’s personal and family history.
Genetic testing for PPAP is available on a clinical basis, both as a stand-alone test and as part of larger panel tests. Mutations in POLD1 and POLE are inherited in an autosomal dominant manner. This means that first degree relatives (parents, siblings, and children) of someone with PPAP have a 50% chance to also have PPAP. Other relatives are at a risk dependent on their degree of relation. Once a mutation has been identified within a family, predictive testing can be offered to at-risk family members.
Although data about PPAP is limited and medical management guidelines have not been established, identifying a POLD1 or POLE mutation may still be beneficial. As mentioned above, family members can be informed and pursue genetic counseling and testing to determine their risk. Knowledge about PPAP will continue to evolve as more people are tested, and additional clinically relevant information will likely be available in the future. Awareness of PPAP in a family may encourage adherence to screening guidelines and close contact with physicians and genetic counselors for updates.
Good candidates for additional genetic testing include:
- Someone with a personal or family history of more than 20 colorectal polyps
- Personal or family history of colorectal cancer diagnosed before age 50
- If you were previously tested for FAP, MAP, or Lynch syndrome and a mutation was not identified
Take the next step:
- To make an appointment with the University of Michigan Cancer Genetics Clinic, please contact 734-763-2532.
- To locate a genetic counselor in your area, visit the National Society of Genetic Counselors website and use the “Find a Genetic Counselor” tool to search by location or specialty.
The University of Michigan Cancer Genetics Clinic provides counseling for people with a personal or family history of cancers that may have genetic links. If a link is confirmed, our specialized physician and genetic counselors will develop a plan for additional screening or lifestyle changes to help reduce cancer risk.
The University of Michigan Comprehensive Cancer Center’s 1,000 doctors, nurses, care givers and researchers are united by one thought: to deliver the highest quality, compassionate care while working to conquer cancer through innovation and collaboration. The center is among the top-ranked national cancer programs, and #1 in Michigan according to U.S. News & World Report. Our multidisciplinary clinics offer one-stop access to teams of specialists for personalized treatment plans, part of the ideal patient care experience. Patients also benefit through access to promising new cancer therapies.