# Polymerase proofreading-associated polyposis

Source: https://onco.cc/terms/polymerase-proofreading-associated-polyposis/  
OnCo record `polymerase-proofreading-associated-polyposis` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Polymerase proofreading-associated polyposis is a rare inherited condition, caused by a fault in the proofreading part of the POLE or POLD1 gene, that causes bowel polyps and early bowel cancer, and womb cancer with POLD1. Care is planned at a specialist centre because there are too few patients for a fixed schedule.

## Summary

Autosomal dominant. Palles 2013 (Nature Genetics) found the high-penetrance heterozygous variants POLE p.Leu424Val and POLD1 p.Ser478Asn in families with multiple adenomas and early colorectal cancer; POLD1 was also associated with endometrial cancer. The tumours are microsatellite stable and hypermutated by base substitutions.

BSG 2020 found insufficient clinical data for specific guidance and recommends referral to a multidisciplinary expert centre (weak recommendation, low evidence). The AACR 2024 update groups it with Lynch syndrome and constitutional mismatch repair deficiency as replication repair deficiency syndromes, and notes aggressive brain tumours in some children with these syndromes and the response of hypermutant cancers to checkpoint immunotherapy.

## Fields

- Kind: Term
- Last checked: 2026-11-04
- Also known as: POLE polyposis; POLD1 polyposis; polymerase proofreading-related polyposis
- Tags: gap-fill; hereditary

## Notes

- Orphanet ORPHA:447877. In the NHS directory it is tested under R211, inherited polyposis.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Polymerase_proofreading-associated_polyposis
- Monahan, Gut 2020: BSG, ACPGBI and UKCGG guidelines for the management of hereditary colorectal cancer: https://doi.org/10.1136/gutjnl-2019-319915
- Das, Clin Cancer Res 2024: DNA replication repair deficiency syndromes in children and young adults (AACR update): https://doi.org/10.1158/1078-0432.ccr-23-3994
- Orphanet ORPHA:447877: https://www.orpha.net/en/disease/detail/447877

## Connected records

- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Endometrial cancer](https://onco.cc/cancers/endometrial/)
- technologies: [Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/)
- targets: [POLD1](https://onco.cc/targets/pold1/), [POLE](https://onco.cc/targets/pole/)
- terms: [Colonoscopy](https://onco.cc/terms/colonoscopy/), [Hereditary cancer syndromes](https://onco.cc/terms/hereditary-cancer-syndromes/)
- key papers: [Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas](https://onco.cc/key-papers/paper-palles-germline-pole-pold1-proofreading-nat-genet-2013/)

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