Assessment of systemic genetic damage in pediatric inflammatory bowel disease. (22nd August 2020)

• Record Type: Journal Article
• Authors: Baig, Ayesha; Avlasevich, Svetlana L.; Torous, Dorothea K.; Bemis, Jeffrey C.; Saubermann, Lawrence J.; Lovell, David P.; MacGregor, James T.; Dertinger, Stephen D.
• Is Part Of: Environmental and molecular mutagenesis. Volume 61:Number 9(2020)
• Page Start: 901
• Page End: 909
• Publication Date: 2020-08-22
• Subjects: chromosomal damage -- genotoxicity; flow cytometry -- inflammatory bowel disease -- mutation; Mutagenesis -- Periodicals; Molecular genetics -- Periodicals; Mutagenèse -- Périodiques; Mutagenèse chimique -- Périodiques; Mutation -- Périodiques; Maladies de l'environnement -- Périodiques; Génétique moléculaire -- Périodiques; 576.542
• DOI: 10.1002/em.22403
• Languages: English
• ISSNs: 0893-6692

Abstract

Abstract: The etiology of distal site cancers in inflammatory bowel disease (IBD) is not well understood and requires further study. We investigated whether pediatric IBD patients' blood cells exhibit elevated levels of genomic damage by measuring the frequency of mutant phenotype (CD59‐/CD55‐) reticulocytes (MUT RET) as a reporter of PIG‐A mutation, and the frequency of micronucleated reticulocytes (MN‐RET) as an indicator of chromosomal damage. IBD patients ( n = 18 new‐onset disease, 46 established disease) were compared to age‐matched controls (constipation or irritable bowel syndrome patients from the same clinic, n = 30) and young healthy adults age 19–24 ( n = 25). IBD patients showed no indication of elevated MUT RET relative to controls (mean ± SD = 3.1 ± 2.3 × 10 −6 vs. 3.6 ± 5.6 x 10 −6, respectively). In contrast, 59 IBD patients where %MN‐RET measurements were obtained, 10 exceeded the upper bound 90% tolerance interval derived from control subjects (i.e., 0.42%). Furthermore, each of the 10 IBD patients with elevated MN‐RET had established disease (10/42), none were new‐onset (0/17) ( p = .049). Interestingly, each of the subjects with increased chromosomal damage was receiving anti‐TNF based monotherapy at the time blood was collected (10/10, 100%), whereas this therapy was less common (20/32, 63%) among patients that exhibited ≤0.42% MN‐RET ( p = .040). The results clearly indicate the need for further work to understand whether the results presented herein are reproducible and if so, to elucidate the causative factor(s) responsible for elevated MN‐RET frequencies in some IBD patients.