Crohn's Disease and Early Exposure to Thiopurines are Independent Risk Factors for Mosaic Chromosomal Alterations in Patients with Inflammatory Bowel Diseases.
Autosomal mosaicism
Crohn’s disease
thiopurines
Journal
Journal of Crohn's & colitis
ISSN: 1876-4479
Titre abrégé: J Crohns Colitis
Pays: England
ID NLM: 101318676
Informations de publication
Date de publication:
10 May 2022
10 May 2022
Historique:
pubmed:
10
11
2021
medline:
14
5
2022
entrez:
9
11
2021
Statut:
ppublish
Résumé
Mosaic chromosomal alterations [mCAs] increase the risk for haematopoietic malignancies and may be risk factors for several other diseases. Inflammatory bowel diseases [IBDs], including Crohn's disease [CD] and ulcerative colitis [UC], are associated with mCAs, and patients may be at risk for haematopoietic malignancy development and/or modification of IBD phenotypes. In the present study, we screened patients with IBD for the presence of mCAs and explored the possible pathophysiological and genetic risk factors for mCAs. We analysed mCAs in peripheral blood from 3339 patients with IBD and investigated the clinical and genetic risk factors for mCAs. CD and exposure to thiopurines before the age of 20 years were identified as novel independent risk factors for mCAs [odds ratio = 2.15 and 5.68, p = 1.17e-2 and 1.60e-3, respectively]. In contrast, there were no significant associations of disease duration, anti-tumour necrosis factor alpha antibodies, or other clinical factors with mCAs. Gene ontology enrichment analysis revealed that genes specifically located in the mCAs in patients with CD were significantly associated with factors related to mucosal immune responses. A genome-wide association study revealed that ERBIN, CD96, and AC068672.2 were significantly associated with mCAs in patients with CD [p = 1.56e-8, 1.65e-8, and 4.92e-8, respectively]. The difference in mCAs between patients with CD and UC supports the higher incidence of haematopoietic malignancies in CD. Caution should be exercised when using thiopurines in young patients with IBD, particularly CD, in light of possible chromosomal alterations.
Sections du résumé
BACKGROUND AND AIMS
OBJECTIVE
Mosaic chromosomal alterations [mCAs] increase the risk for haematopoietic malignancies and may be risk factors for several other diseases. Inflammatory bowel diseases [IBDs], including Crohn's disease [CD] and ulcerative colitis [UC], are associated with mCAs, and patients may be at risk for haematopoietic malignancy development and/or modification of IBD phenotypes. In the present study, we screened patients with IBD for the presence of mCAs and explored the possible pathophysiological and genetic risk factors for mCAs.
METHODS
METHODS
We analysed mCAs in peripheral blood from 3339 patients with IBD and investigated the clinical and genetic risk factors for mCAs.
RESULTS
RESULTS
CD and exposure to thiopurines before the age of 20 years were identified as novel independent risk factors for mCAs [odds ratio = 2.15 and 5.68, p = 1.17e-2 and 1.60e-3, respectively]. In contrast, there were no significant associations of disease duration, anti-tumour necrosis factor alpha antibodies, or other clinical factors with mCAs. Gene ontology enrichment analysis revealed that genes specifically located in the mCAs in patients with CD were significantly associated with factors related to mucosal immune responses. A genome-wide association study revealed that ERBIN, CD96, and AC068672.2 were significantly associated with mCAs in patients with CD [p = 1.56e-8, 1.65e-8, and 4.92e-8, respectively].
CONCLUSIONS
CONCLUSIONS
The difference in mCAs between patients with CD and UC supports the higher incidence of haematopoietic malignancies in CD. Caution should be exercised when using thiopurines in young patients with IBD, particularly CD, in light of possible chromosomal alterations.
Identifiants
pubmed: 34751398
pii: 6423962
doi: 10.1093/ecco-jcc/jjab199
doi:
Substances chimiques
Immunologic Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
643-655Subventions
Organisme : Japan Agency for Medical Research and Development
ID : 20ek0410056
Organisme : Japan Society for the Promotion of Science
ID : JP15H04805
Investigateurs
Hirotake Sakuraba
(H)
Yoh Ishiguro
(Y)
Ryota Hokari
(R)
Hiroshi Araki
(H)
Satoshi Motoya
(S)
Taku Kobayashi
(T)
Atsushi Nishida
(A)
Kentaro Ikeya
(K)
Shoko Nakagawa
(S)
Miki Miura
(M)
Takahiko Toyonaga
(T)
Kei Onodera
(K)
Shunji Ishihara
(S)
Naoki Oshima
(N)
Takehiko Katsurada
(T)
Yu Sasaki
(Y)
Takafumi Otsuka
(T)
Mikihiro Fujiya
(M)
Shinta Mizuno
(S)
Makoto Naganuma
(M)
Toshimitsu Fujii
(T)
Masakazu Nagahori
(M)
Katsuhiro Arai
(K)
Mitsunori Noguchi
(M)
Minoru Matsuura
(M)
Yuki Ohta
(Y)
Tomoo Nakagawa
(T)
Masahiro Takahara
(M)
Sakiko Hiraoka
(S)
Masaru Shinozaki
(M)
Yasuo Suzuki
(Y)
Katsuyoshi Matsuoka
(K)
Motohiro Esaki
(M)
Akira Harada
(A)
Koji Ikegami
(K)
Hideaki Ohyama
(H)
Kai Korekawa
(K)
Sayumi Takahashi
(S)
Motoki Makuuchi
(M)
Yushi Inomata
(Y)
Fumiko Shimoda
(F)
Takahiro Takahashi
(T)
Kota Yano
(K)
Izuru Abe
(I)
Tomoyuki Handa
(T)
Yutaro Masu
(Y)
Kaoru Suzuki
(K)
Kasumi Hishinuma
(K)
Yoshitake Kanazawa
(Y)
Tomoya Kimura
(T)
Katsuya Endo
(K)
Kenichi Negoro
(K)
Mai Kato
(M)
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.