Defining absolute postoperative desmoid risk in familial adenomatous polyposis according to APC genotype and family history: retrospective cohort study
Author(s)
Zare, Benjamin
Bahar, Massih
Clark, Susan
Latchford, Andrew
Zare, Ben
Type
Journal Article
Abstract
Introduction
Desmoid disease is a major cause of morbidity and mortality in familial adenomatous polyposis (FAP), particularly following prophylactic colorectal surgery. Although APC genotype and family history are recognised risk factors, prior sizeable studies report relative rather than absolute risks. This study aimed to quantify absolute post-operative desmoid risk in FAP patients undergoing risk-reducing colectomy, stratified by APC genotype, and to assess the modifying effect of family history.
Method
Retrospective observational study using records from a prospectively maintained registry. Patients with an APC pathogenic variant (PV) 3′ of codon 1399 were classified as high-risk, and those 5′ of (or at) codon 1399 as low risk. Patients who had not undergone prophylactic colectomy, with <5 years of post-operative follow-up, or with a desmoid diagnosed before or at the time of surgery were excluded. Clinical records were reviewed for details of surgery, desmoid diagnosis, and family history. A positive family history was defined as a first-degree relative with genetically confirmed FAP and a diagnosis of desmoid disease (clinical and/or radiological).
Results
Among 48 high-risk patients, 30 (63%) developed desmoid, with no significant difference between colectomy and proctocolectomy (63% vs 69%; p=0.56). Family history was present in 35/48 (73%) and increased risk (80% with family history vs 15% without; p<0.01). Among 1213 low-risk patients, 154 (13%) developed desmoids, with no significant effect of surgical procedure (14% vs 11%; p=0.12). Family history increased risk (30% vs 10%; p<0.01).
Conclusion
Family history of desmoid disease appears to be an important determinant of post-operative desmoid risk in FAP. Although APC PV 3′ of codon 1399 does confer a high overall risk, this is largely confined to those with first-degree relatives with desmoid. In the absence of a family history, postoperative desmoid risk appeared relatively low irrespective of genotype. This supports a more individualised approach to peri-operative counselling and surgical decision-making in patients with FAP. Additionally, these data highlight patients with both a 3' APC PV and a positive family history as a particularly high-risk subgroup who may represent an appropriate target population for future chemoprevention trials.
Desmoid disease is a major cause of morbidity and mortality in familial adenomatous polyposis (FAP), particularly following prophylactic colorectal surgery. Although APC genotype and family history are recognised risk factors, prior sizeable studies report relative rather than absolute risks. This study aimed to quantify absolute post-operative desmoid risk in FAP patients undergoing risk-reducing colectomy, stratified by APC genotype, and to assess the modifying effect of family history.
Method
Retrospective observational study using records from a prospectively maintained registry. Patients with an APC pathogenic variant (PV) 3′ of codon 1399 were classified as high-risk, and those 5′ of (or at) codon 1399 as low risk. Patients who had not undergone prophylactic colectomy, with <5 years of post-operative follow-up, or with a desmoid diagnosed before or at the time of surgery were excluded. Clinical records were reviewed for details of surgery, desmoid diagnosis, and family history. A positive family history was defined as a first-degree relative with genetically confirmed FAP and a diagnosis of desmoid disease (clinical and/or radiological).
Results
Among 48 high-risk patients, 30 (63%) developed desmoid, with no significant difference between colectomy and proctocolectomy (63% vs 69%; p=0.56). Family history was present in 35/48 (73%) and increased risk (80% with family history vs 15% without; p<0.01). Among 1213 low-risk patients, 154 (13%) developed desmoids, with no significant effect of surgical procedure (14% vs 11%; p=0.12). Family history increased risk (30% vs 10%; p<0.01).
Conclusion
Family history of desmoid disease appears to be an important determinant of post-operative desmoid risk in FAP. Although APC PV 3′ of codon 1399 does confer a high overall risk, this is largely confined to those with first-degree relatives with desmoid. In the absence of a family history, postoperative desmoid risk appeared relatively low irrespective of genotype. This supports a more individualised approach to peri-operative counselling and surgical decision-making in patients with FAP. Additionally, these data highlight patients with both a 3' APC PV and a positive family history as a particularly high-risk subgroup who may represent an appropriate target population for future chemoprevention trials.
Date Acceptance
2026-05-26
Citation
BJS Open
ISSN
2474-9842
Publisher
Oxford University Press
Journal / Book Title
BJS Open
Copyright Statement
Copyright This paper is embargoed until publication. Once published the Version of Record (VoR) will be available on immediate open access.
License URL
Publication Status
Accepted