Dataset Information

Somatic Evolution in Non-neoplastic IBD-Affected Colon.

ABSTRACT: Inflammatory bowel disease (IBD) is a chronic inflammatory disease associated with increased risk of gastrointestinal cancers. We whole-genome sequenced 446 colonic crypts from 46 IBD patients and compared these to 412 crypts from 41 non-IBD controls from our previous publication on the mutation landscape of the normal colon. The average mutation rate of affected colonic epithelial cells is 2.4-fold that of healthy colon, and this increase is mostly driven by acceleration of mutational processes ubiquitously observed in normal colon. In contrast to the normal colon, where clonal expansions outside the confines of the crypt are rare, we observed widespread millimeter-scale clonal expansions. We discovered non-synonymous mutations in ARID1A, FBXW7, PIGR, ZC3H12A, and genes in the interleukin 17 and Toll-like receptor pathways, under positive selection in IBD. These results suggest distinct selection mechanisms in the colitis-affected colon and that somatic mutations potentially play a causal role in IBD pathogenesis.

SUBMITTER: Olafsson S

PROVIDER: S-EPMC7427325 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Publications

Somatic Evolution in Non-neoplastic IBD-Affected Colon.

Olafsson Sigurgeir S McIntyre Rebecca E RE Coorens Tim T Butler Timothy T Jung Hyunchul H Robinson Philip S PS Lee-Six Henry H Sanders Mathijs A MA Arestang Kenneth K Dawson Claire C Tripathi Monika M Strongili Konstantina K Hooks Yvette Y Stratton Michael R MR Parkes Miles M Martincorena Inigo I Raine Tim T Campbell Peter J PJ Anderson Carl A CA

Cell 20200721 3

Inflammatory bowel disease (IBD) is a chronic inflammatory disease associated with increased risk of gastrointestinal cancers. We whole-genome sequenced 446 colonic crypts from 46 IBD patients and compared these to 412 crypts from 41 non-IBD controls from our previous publication on the mutation landscape of the normal colon. The average mutation rate of affected colonic epithelial cells is 2.4-fold that of healthy colon, and this increase is mostly driven by acceleration of mutational processes ...[more]

PMID: 32697969

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Project description:BackgroundInflammatory bowel disease (IBD) is an emerging disease in Hispanics. In this study, we examine the prevalence of IBD-related colon dysplasia (IBD-dys) in Hispanics versus non-Hispanic whites (NHWs) and compare differences in established clinical and environmental risk factors.MethodsWe performed a cross-sectional analysis on adult Hispanics and NHWs with IBD who met criteria for colorectal cancer surveillance and were followed at our center between 2008 and 2018. Clinical variables and IBD phenotype were recorded. Lifestyle IBD-dys risk factors were examined, including smoking and lack of physical activity. Using multivariable regression, we compared the prevalence of IBD-dys in Hispanics versus NHW, using relevant covariates. Receiver operating characteristic and area under the curve were performed to find the best fitting model.ResultsA total of 445 IBD patients were included (148 Hispanics and 297 NHWs). IBD phenotype was similar between groups, except that Hispanics had shorter disease duration, a lower frequency of Crohn's disease-related complications, and lower reported use of steroids. Frequency of surveillance colonoscopies was similar between Hispanics and NHW. There were no differences in median body mass index between Hispanics and NHW [26.5 (IQR 6.0) vs 25.0 (IQR 6.0), P = 0.40]. Hispanics were less likely than NHW to consume alcohol but smoking history was similar between groups. Three out of 148 Hispanic patients had IBD-dys (2.02%) compared to 29 out of 297 NHWs (9.76%). Adjusting for disease duration, primary sclerosing cholangitis, family history of colon cancer, and smoking, Hispanics had a lower prevalence of IBD-dys compared to NHW [ORadjusted = 0.207 (95% CI 0.046-0.938), P = 0.008].ConclusionsHispanics with IBD undergoing surveillance had a lower prevalence of IBD-dys than their NHW counterparts, despite similar risk factors. Future studies should examine dietary and microbial factors that may explain differences in risk.

Dataset Information

Somatic Evolution in Non-neoplastic IBD-Affected Colon.

Publications

Somatic Evolution in Non-neoplastic IBD-Affected Colon.

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