POLD1 Gene Mutations

Polymerase Proofreading-associated Syndrome (PPAS)

POLD1 ASSOCIATED CANCER RISKS

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Additional Information

POLD1 gene

Associated Syndrome Name: Polymerase Proofreading-associated Syndrome (PPAS)

POLD1 Summary Cancer Risk Table

Cancer Genetic Cancer Risk
ColorectalElevated Risk

POLD1 gene Overview

Polymerase Proofreading-associated Syndrome (PPAS) 1, 2, 3
  • POLD1 mutations have been found in individuals with early onset colorectal cancer, large numbers of adenomatous colorectal polyps, and/or significant family histories of colorectal cancer. Although there are as yet no precise estimates of the colorectal cancer risk associated with mutations in POLD1, it is believed that the risk is significantly increased over that in the general population.
  • Some families with POLD1 mutations include individuals with a wide range of other cancers. In particular, there is some evidence for an increased risk for endometrial cancer in women with mutations in POLD1. Further studies are needed to determine which cancers are conclusively associated with POLD1 gene mutations.
  • Although there is an increased risk for colorectal cancer in individuals with PPAS due to mutations in POLD1, it may be possible to reduce this risk with appropriate medical management. Guidelines for the medical management of patients with PPAS have been developed by the National Comprehensive Cancer Network (NCCN). These are listed below. These guidelines will evolve as we learn more about PPAS, and it is recommended that patients with a POLD1 mutation and a diagnosis of PPAS be managed by a multidisciplinary team with expertise in medical genetics and the care of patients with hereditary cancer syndromes.

POLD1 gene Cancer Risk Table

Cancer Type Age Range Cancer Risk Risk for General Population
ColorectalTo age 801, 2, 3, 4Elevated risk3.0%

POLD1 Cancer Risk Management Table

The overview of medical management options provided is a summary of professional society guidelines. The most recent version of each guideline should be consulted for more detailed and up-to-date information before developing a treatment plan for a particular patient.

This overview is provided for informational purposes only and does not constitute a recommendation. While the medical society guidelines summarized herein provide important and useful information, medical management decisions for any particular patient should be made in consultation between that patient and his or her healthcare provider and may differ from society guidelines based on a complete understanding of the patient’s personal medical history, surgeries and other treatments.

Cancer Type Procedure Age to Begin Frequency
(Unless otherwise indicated by findings)
ColorectalColonoscopy125 to 30 yearsEvery 2 to 3 years
Colorectal surgical evaluation and counseling.1Based on cancer diagnosis and/or polyp number, size and histologyNA

Information for Family Members

The following information for Family Members will appear as part of the MMT for a patient found to have a mutation in the POLD1 gene.

A major potential benefit of myRisk genetic testing for hereditary cancer risk is the opportunity to prevent cancer in relatives of patients in whom clinically significant mutations are identified. Healthcare providers have an important role in making sure that patients with clinically significant mutations are informed about the risks to relatives, and ways in which genetic testing can guide lifesaving interventions.

References

  1. Provenzale D, et al. NCCN Clinical Practice Guidelines in Oncology® Genetic/Familial High-Risk Assessment: Colorectal. V 3.2019. Dec 13. Available at http://www.nccn.org.
  2. Bellido F, et al. POLE and POLD1 mutations in 529 kindred with familial colorectal cancer and/or polyposis: review of reported cases and recommendations for genetic testing and surveillance. Genet Med. 2015 18:325-332. PMID: 26133394.
  3. Palles C, et al. Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas. Nat Genet. 2013 45:136-44. PMID: 23263490.
  4. Fast Stats: An interactive tool for access to SEER cancer statistics. Surveillance Research Program, National Cancer Institute. https://seer.cancer.gov/faststats. (Accessed on 1-2-2017)
Last Updated on 10-Dec-2020