Evidence map›Paper›PMID 33948826›Full record

ArticleFamilial cancer2022

The clinical features of polymerase proof-reading associated polyposis (PPAP) and recommendations for patient management.

Claire Palles, Lynn Martin, Enric Domingo, Laura Chegwidden, Josh McGuire, Vicky Cuthill, Ellen Heitzer, CORGI Consortium, Rachel Kerr, David Kerr and 4 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Familial cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 2 pooled it
7.0field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

45 citing papers in PubMed, 2 syntheses or guidelines pooled it, 68 citations in OpenAlex.

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  12. Genetic predisposition to polyposis syndromes.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025
    Review
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  17. Case Report: Expansion of theFrontiers in oncology · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 7 institutions in 2 countries.

Claire PallesGastrointestinal Cancer Genetics Laboratory, Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT, UK. c.palles@bham.ac.uk.ORCID 0000-0002-9670-2263
Lynn MartinEdinburgh Cancer Research Centre, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh, EH4 2XU, UK.
Enric DomingoDepartment of Oncology, Old Road Campus Research Building, University of Oxford, Roosevelt Drive, Oxford, UK.
Laura ChegwiddenGastrointestinal Cancer Genetics Laboratory, Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT, UK.
Josh McGuireWellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK.
Vicky CuthillPolyposis Registry, St Mark's Hospital, Harrow, London, HA1 3UJ, UK.
Ellen HeitzerDiagnostic and Research Institute of Human Genetics, University of Gratz, Graz, Austria.
CORGI Consortium
Rachel KerrDepartment of Oncology, Old Road Campus Research Building, University of Oxford, Roosevelt Drive, Oxford, UK.
David KerrNuffield Department of Clinical Laboratory Sciences, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
Stephen KearseyZRAB, University of Oxford, 11a Mansfield Road, Oxford, OX1 3SZ, UK.
Susan K ClarkPolyposis Registry, St Mark's Hospital, Harrow, London, HA1 3UJ, UK.
Ian TomlinsonEdinburgh Cancer Research Centre, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh, EH4 2XU, UK.
Andrew LatchfordPolyposis Registry, St Mark's Hospital, Harrow, London, HA1 3UJ, UK.
St Mark's Hospital · GBUniversity of Oxford · GBEdinburgh Cancer Research · GBUniversity of Birmingham · GBCentre for Human Genetics · GBJohn Radcliffe Hospital · GBUniversity of Graz · AT

Funding

Cancer Research UK 27327
6 · The paper itself

Abstract

Pathogenic germline exonuclease domain (ED) variants of POLE and POLD1 cause the Mendelian dominant condition polymerase proof-reading associated polyposis (PPAP). We aimed to describe the clinical features of all PPAP patients with probably pathogenic variants. We identified patients with a variants mapping to the EDs of POLE or POLD1 from cancer genetics clinics, a colorectal cancer (CRC) clinical trial, and systematic review of the literature. We used multiple evidence sources to separate ED variants into those with strong evidence of pathogenicity and those of uncertain importance. We performed quantitative analysis of the risk of CRC, colorectal adenomas, endometrial cancer or any cancer in the former group. 132 individuals carried a probably pathogenic ED variant (105 POLE, 27 POLD1). The earliest malignancy was colorectal cancer at 14. The most common tumour types were colorectal, followed by endometrial in POLD1 heterozygotes and duodenal in POLE heterozygotes. POLD1-mutant cases were at a significantly higher risk of endometrial cancer than POLE heterozygotes. Five individuals with a POLE pathogenic variant, but none with a POLD1 pathogenic variant, developed ovarian cancer. Nine patients with POLE pathogenic variants and one with a POLD1 pathogenic variant developed brain tumours. Our data provide important evidence for PPAP management. Colonoscopic surveillance is recommended from age 14 and upper-gastrointestinal surveillance from age 25. The management of other tumour risks remains uncertain, but surveillance should be considered. In the absence of strong genotype-phenotype associations, these recommendations should apply to all PPAP patients.

Indexed as

Colorectal NeoplasmsEndometrial NeoplasmsDNA Polymerase IIFemaleGerm-Line MutationHumansPoly-ADP-Ribose Binding ProteinsPropylaminesDNA Polymerase IIN-(3-phenyl-n-propyl)-1-phenyl-2-aminopropanePoly-ADP-Ribose Binding ProteinsPropylaminesExonuclease domain mutationPOLD1POLEPPAP

Identifiers

PMID33948826
PMCPMC8964588
OpenAlexW3158210605

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.