AXIN2 germline testing in a French cohort validates pathogenic variants as a rare cause of predisposition to colorectal polyposis and cancer - Université Paris Cité Accéder directement au contenu
Article Dans Une Revue Genes, Chromosomes & Cancer Année : 2023

AXIN2 germline testing in a French cohort validates pathogenic variants as a rare cause of predisposition to colorectal polyposis and cancer

Marie Beaumont
Roseline Vibert
Stéphane Pinson
Catherine Vermaut
Cathy Flament
  • Fonction : Auteur
Tonio Lovecchio
  • Fonction : Auteur
Lucie Delattre
  • Fonction : Auteur
Christophe Demay
  • Fonction : Auteur
Florence Coulet
Erell Guillerm
  • Fonction : Auteur
Nadim Hamzaoui
Patrick Benusiglio
Afane Brahimi
  • Fonction : Auteur
François Cornelis
  • Fonction : Auteur
Hélène Delhomelle
  • Fonction : Auteur
Sandra Fert-Ferrer
  • Fonction : Auteur
Clémentine Legrand
Alain Lortholary
David Malka
Florence Petit
Jean‐christophe Saurin
Sophie Lejeune
Chrystelle Colas

Résumé

Only a few patients with germline AXIN2 variants and colorectal adenomatous polyposis or cancer have been described, raising questions about the actual contribution of this gene to colorectal cancer (CRC) susceptibility. To assess the clinical relevance for AXIN2 testing in patients suspected of genetic predisposition to CRC, we collected clinical and molecular data from the French Oncogenetics laboratories analyzing AXIN2 in this context. Between 2004 and June 2020, 10 different pathogenic/likely pathogenic AXIN2 variants were identified in 11 unrelated individuals. Eight variants were from a consecutive series of 3322 patients, which represents a frequency of 0.24%. However, loss‐of‐function AXIN2 variants were strongly associated with genetic predisposition to CRC as compared with controls (odds ratio: 11.89, 95% confidence interval: 5.103–28.93). Most of the variants were predicted to produce an AXIN2 protein devoid of the SMAD3‐binding and DIX domains, but preserving the β‐catenin‐binding domain. Ninety‐one percent of the AXIN2 variant carriers who underwent colonoscopy had adenomatous polyposis. Forty percent of the variant carriers developed colorectal or/and other digestive cancer. Multiple tooth agenesis was present in at least 60% of them. Our report provides further evidence for a role of AXIN2 in CRC susceptibility, arguing for AXIN2 testing in patients with colorectal adenomatous polyposis or cancer.

Dates et versions

hal-04090128 , version 1 (05-05-2023)

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Paternité - Pas d'utilisation commerciale - Pas de modification

Identifiants

Citer

Julie Leclerc, Marie Beaumont, Roseline Vibert, Stéphane Pinson, Catherine Vermaut, et al.. AXIN2 germline testing in a French cohort validates pathogenic variants as a rare cause of predisposition to colorectal polyposis and cancer. Genes, Chromosomes & Cancer, 2023, 62 (4), pp.210-222. ⟨10.1002/gcc.23112⟩. ⟨hal-04090128⟩
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