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POLD1 gene - Cancer risk, management, and testing for genetic mutations

Associated Syndrome Name: Polymerase proofreading-associated polyposis (PPAP)

POLD1 Summary Cancer Risk Table

Cancer	Genetic Cancer Risk
Colorectal	High Risk
Endometrial	Elevated Risk
Other	Elevated Risk

POLD1 gene Overview

Polymerase proofreading-associated polyposis (PPAP) 1, 2, 3, 4, 5

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, including some with multiple primary tumors. 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 PPAP 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 PPAP have been developed by the National Comprehensive Cancer Network (NCCN). These are listed below. These guidelines will evolve as we learn more about PPAP, and it is recommended that patients with a POLD1 mutation and a diagnosis of PPAP 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
Colorectal	To age 701, 2, 3, 4, 5, 6	50%	1.8%
Endometrial	To age 701	Elevated risk	1.9%
Small Bowel	To age 701	Possibly elevated risk	0.1%

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)
Colorectal	Colonoscopy3	25 to 30 years, or 2 to 5 years younger than the earliest colorectal cancer diagnosis in the family if it is under age 25	Every 2 to 3 years
	Colorectal surgical evaluation and counseling.3	Based on cancer diagnosis and/or polyp number, size and histology	NA
Endometrial	Patient education about the importance of quickly seeking attention for endometrial cancer symptoms, such as abnormal bleeding.3	Individualized	NA
	Consider transvaginal ultrasound.3	After menopause	Individualized
Small Bowel	Upper endoscopy3	Baseline at 30 to 35 years, or earlier if there is a family history of small bowel cancer	Based on polyp number, size and histology

Benefits of Testing for POLD1 Gene Mutations:

Testing for POLD1 gene mutations with the MyRisk^® Hereditary Cancer Test with RiskScore^® provides critical insights to patients and providers about potential hereditary cancer risk. Identifying a POLD1 gene mutation can help clarify whether a patient is at increased risk for certain cancers and guide proactive, personalized care planning. With definitive answers from the MyRisk Test, healthcare providers can better tailor screening, prevention, and management strategies, while patients gain clarity and confidence about their hereditary cancer risk. In addition, understanding a POLD1 gene mutation allows family members to consider their own hereditary cancer risk, supporting informed decision-making and potentially life-saving early interventions. Learn more about the MyRisk^® with RiskScore^® Hereditary Cancer Test.

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.

This patient's relatives are at risk for carrying the same mutation(s) and associated cancer risks as this patient. Cancer risks for females and males who have this/these mutation(s) are provided below.

Family members should talk to a healthcare provider about genetic testing. Close relatives such as parents, children, brothers and sisters have the highest chance of having the same mutation(s) as this patient. Other more distant relatives such as cousins, aunts, uncles, and grandparents also have a chance of carrying the same mutation(s). Testing of at-risk relatives can identify those family members with the same mutation(s) who may benefit from surveillance and early intervention.

References

Palles C, et al. The clinical features of polymerase proof-reading associated polyposis (PPAP) and recommendations for patient management. Fam Cancer. 2022 21:197-209. PMID: 33948826.

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.

Gupta S, et al. NCCN Clinical Practice Guidelines in Oncology^® Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric. V 1.2025. Jun 13. Available at https://www.nccn.org.

Buchanan DD, et al. Risk of colorectal cancer for carriers of a germ-line mutation in POLE or POLD1. Genet Med. 2018 20:890-895. Erratum in: Genet Med. 2018 Feb 01. PMID: 29120461.

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.

SEER*Explorer: An interactive website for SEER cancer statistics [Internet]. Surveillance Research Program, National Cancer Institute. [Cited 2025 Aug 12]. Available from https://seer.cancer.gov/explorer/.

Last Updated on 15-Sep-2025