The diagnostic yield of genetic testing in patients with multiple colorectal adenomas: a specialist centre cohort study
File(s)
Published version
Author(s)
Sau, Mak
Alexander, James
Clark, Susan
Latchford, Andrew
Monahan, kevin
Type
Journal Article
Abstract
INTRODUCTION:
Adenoma multiplicity is associated with increased colorectal cancer (CRC) risk. The utility of genetic testing in patients with multiple colorectal adenomas (MCRA) remains uncertain. We evaluated the diagnostic yield of mutations in polyposis- and CRC-associated genes in patients with MCRA.
METHODS:
We performed a cross-sectional review of adult patients with 10–99 cumulative adenomas from the prospective database at the St Mark's Hospital Polyposis Registry and Family Cancer Clinic between 1999 and 2021. Genetic testing was performed for adenomatous polyposis–associated genes, hamartomatous polyposis–associated genes, and nonpolyposis colorectal cancer–associated genes. Clinicopathological outcomes were extracted for multiple logistic regression analysis.
RESULTS:
Two hundred fifty-nine patients with MCRA (median age 61 [interquartile range 53–69] years) were identified. Sixty-six patients (25.5%) had a pathogenic variant or likely pathogenic variant, with APC and biallelic MUTYH mutations constituting the majority of identified pathogenic variant/likely pathogenic variants. Diagnostic yields were greater than 10% at any adenoma burden. In univariate analysis, higher adenoma burden and younger age were associated with higher yield (both P < 0.0001). In patients with MCRA with 10–19 adenomas without a relevant personal or family history of CRC, the diagnostic yield was nil. In multiple logistic regression analysis, higher adenoma burden, younger age, personal history of CRC, and first-degree familial history of CRC were associated with higher diagnostic yield.
DISCUSSION:
Diagnostic yield of >10% at any adenoma burden supports current guidance for constitutional genetic testing in patients with MCRA, although the low yield in people older than 60 years with 10–19 adenomas suggests that a stratified approach might be appropriate.
Adenoma multiplicity is associated with increased colorectal cancer (CRC) risk. The utility of genetic testing in patients with multiple colorectal adenomas (MCRA) remains uncertain. We evaluated the diagnostic yield of mutations in polyposis- and CRC-associated genes in patients with MCRA.
METHODS:
We performed a cross-sectional review of adult patients with 10–99 cumulative adenomas from the prospective database at the St Mark's Hospital Polyposis Registry and Family Cancer Clinic between 1999 and 2021. Genetic testing was performed for adenomatous polyposis–associated genes, hamartomatous polyposis–associated genes, and nonpolyposis colorectal cancer–associated genes. Clinicopathological outcomes were extracted for multiple logistic regression analysis.
RESULTS:
Two hundred fifty-nine patients with MCRA (median age 61 [interquartile range 53–69] years) were identified. Sixty-six patients (25.5%) had a pathogenic variant or likely pathogenic variant, with APC and biallelic MUTYH mutations constituting the majority of identified pathogenic variant/likely pathogenic variants. Diagnostic yields were greater than 10% at any adenoma burden. In univariate analysis, higher adenoma burden and younger age were associated with higher yield (both P < 0.0001). In patients with MCRA with 10–19 adenomas without a relevant personal or family history of CRC, the diagnostic yield was nil. In multiple logistic regression analysis, higher adenoma burden, younger age, personal history of CRC, and first-degree familial history of CRC were associated with higher diagnostic yield.
DISCUSSION:
Diagnostic yield of >10% at any adenoma burden supports current guidance for constitutional genetic testing in patients with MCRA, although the low yield in people older than 60 years with 10–19 adenomas suggests that a stratified approach might be appropriate.
Date Issued
2024-01
Date Acceptance
2023-09-19
Citation
Clinical and Translational Gastroenterology, 2024, 15 (1)
ISSN
2155-384X
Publisher
Wolters Kluwer
Journal / Book Title
Clinical and Translational Gastroenterology
Volume
15
Issue
1
Copyright Statement
© 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology Open Access This is an open-access article distributed under the terms of the
Creative Commons Attribution-Non Commercial-No Derivatives License 4.0
(CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used
commercially without permission from the journal.
Creative Commons Attribution-Non Commercial-No Derivatives License 4.0
(CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used
commercially without permission from the journal.
Identifier
https://journals.lww.com/ctg/fulltext/2024/01000/the_diagnostic_yield_of_genetic_testing_in.10.aspx
Publication Status
Published
Article Number
e00645
Date Publish Online
2023-10-10