Inflammation and Cancer IV. Colorectal cancer in inflammatory bowel disease: the role of inflammation

2004 ◽  
Vol 287 (1) ◽  
pp. G7-G17 ◽  
Author(s):  
Steven H. Itzkowitz ◽  
Xianyang Yio
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Colonic Mucosa ◽  
Normal Colonic Mucosa ◽  
Sporadic Colorectal Cancer ◽  
Increased Risk ◽  
Inflammatory Bowel ◽  
Repair Genes

Patients with ulcerative colitis and Crohn's disease are at increased risk for developing colorectal cancer. To date, no known genetic basis has been identified to explain colorectal cancer predisposition in these inflammatory bowel diseases. Instead, it is assumed that chronic inflammation is what causes cancer. This is supported by the fact that colon cancer risk increases with longer duration of colitis, greater anatomic extent of colitis, the concomitant presence of other inflammatory manifestations such as primary sclerosing cholangitis, and the fact that certain drugs used to treat inflammation, such as 5-aminosalicylates and steroids, may prevent the development of colorectal cancer. The major carcinogenic pathways that lead to sporadic colorectal cancer, namely chromosomal instability, microsatellite instability, and hypermethylation, also occur in colitis-associated colorectal cancers. Unlike normal colonic mucosa, however, inflamed colonic mucosa demonstrates abnormalities in these molecular pathways even before any histological evidence of dysplasia or cancer. Whereas the reasons for this are unknown, oxidative stress likely plays a role. Reactive oxygen and nitrogen species produced by inflammatory cells can interact with key genes involved in carcinogenic pathways such as p53, DNA mismatch repair genes, and even DNA base excision-repair genes. Other factors such as NF-κB and cyclooxygenases may also contribute. Administering agents that cause colitis in healthy rodents or genetically engineered cancer-prone mice accelerates the development of colorectal cancer. Mice genetically prone to inflammatory bowel disease also develop colorectal cancer especially in the presence of bacterial colonization. These observations offer compelling support for the role of inflammation in colon carcinogenesis.

scholarly journals Inflammatory Bowel Disease and Risk of Colorectal Cancer: An Overview From Pathophysiology to Pharmacological Prevention

2021 ◽  
Vol 12 ◽  
Author(s):  
Marianna Lucafò ◽  
Debora Curci ◽  
Martina Franzin ◽  
Giuliana Decorti ◽  
Gabriele Stocco
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Inflammatory Process ◽  
Current Knowledge ◽  
Genetic Alterations ◽  
Pharmacological Prevention ◽  
Increased Risk ◽  
Inflammatory Bowel

Increased risk of colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients has been attributed to long-standing chronic inflammation, with the contribution of genetic alterations and environmental factors such as the microbiota. Moreover, accumulating data indicate that IBD-associated CRC (IBD-CRC) may initiate and develop through a pathway of tumorigenesis distinct from that of sporadic CRC. This mini-review summarizes the current knowledge of IBD-CRC, focusing on the main mechanisms underlying its pathogenesis, and on the important role of immunomodulators and biologics used to treat IBD patients in interfering with the inflammatory process involved in carcinogenesis.

37 Monitoring the evolution of inflammatory bowel disease (IBD) in pediatric and adult cohorts of patients to identify biomarkers to predict cancer risk

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A38-A38
Author(s):  
Shilpa Ravindran ◽  
Heba Sidahmed ◽  
Harshitha Manjunath ◽  
Rebecca Mathew ◽  
Tanwir Habib ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Mesenchymal Transition ◽  
Increased Risk ◽  
Hamad Medical Corporation ◽  
Inflammatory Bowel ◽  
Left And Right

BackgroundPatients with inflammatory bowel disease (IBD) have increased risk of developing colorectal cancer (CRC), depending on the duration and severity of the disease. The evolutionary process in IBD is driven by chronic inflammation leading to epithelial-to-mesenchymal transition (EMT) events in colonic fibrotic areas. EMT plays a determinant role in tumor formation and progression, through the acquisition of ‘stemness’ properties and the generation of neoplastic cells. The aim of this study is to monitor EMT/cancer initiating tracts in IBD in association with the deep characterization of inflammation in order to assess the mechanisms of IBD severity and progression towards malignancy.Methods10 pediatric and 20 adult IBD patients, admitted at Sidra Medicine (SM) and Hamad Medical Corporation (HMC) respectively, have been enrolled in this study, from whom gut tissue biopsies (from both left and right side) were collected. Retrospectively collected tissues (N=10) from patients with malignancy and history of IBD were included in the study. DNA and RNA were extracted from fresh small size (2–4 mm in diameter) gut tissues using the BioMasher II (Kimble) and All Prep DNA/RNA kits (Qiagen). MicroRNA (miRNA; N=700) and gene expression (N=800) profiling have been performed (cCounter platform; Nanostring) as well as the methylation profiling microarray (Infinium Methylation Epic Bead Chip kit, Illumina) to interrogate up to 850,000 methylation sites across the genome.ResultsDifferential miRNA profile (N=27 miRNA; p<0.05) was found by the comparison of tissues from pediatric and adult patients. These miRNAs regulate: i. oxidative stress damage (e.g., miR 99b), ii. hypoxia induced autophagy; iii. genes associated with the susceptibility to IBD (ATG16L1, NOD2, IRGM), iv. immune responses, such as TH17 T cell subset (miR 29). N=6 miRNAs (miR135b, 10a196b, 125b, let7c, 375) linked with the regulation of Wnt/b-catenin, EM-transaction, autophagy, oxidative stress and play role also in cell proliferation and mobilization and colorectal cancer development were differentially expressed (p<0.05) in tissues from left and right sides of gut. Gene expression signature, including genes associated with inflammation, stemness and fibrosis, has also been performed for the IBD tissues mentioned above. Methylation sites at single nucleotide resolution have been analyzed.ConclusionsAlthough the results warrant further investigation, differential genomic profiling suggestive of altered pathways involved in oxidative stress, EMT, and of the possible stemness signature was found. The integration of data from multiple platforms will provide insights of the overall molecular determinants in IBD patients along with the evolution of the disease.Ethics ApprovalThis study was approved by Sidra Medicine and Hamad Medical Corporation Ethics Boards; approval number 180402817 and MRC-02-18-096, respectively.

Ethnic Differences in the Smoking-Related Risk of Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

2021 ◽  
Author(s):  
Daniele Piovani ◽  
Claudia Pansieri ◽  
Soumya R R Kotha ◽  
Amanda C Piazza ◽  
Celia-Louise Comberg ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Latin American ◽  
Bowel Disease ◽  
Meta Analysis ◽  
Study Data ◽  
Future Research ◽  
Related Risk ◽  
Increased Risk ◽  
Inflammatory Bowel

Abstract Background and aims The association between smoking and inflammatory bowel disease (IBD) relies on old meta-analyses including exclusively non-Jewish White populations. Uncertainty persists regarding the role of smoking in other ethnicities. Methods We systematically searched Medline/PubMed, Embase and Scopus for studies examining tobacco smoking and the risk of developing IBD, i.e., Crohn’s disease (CD) or ulcerative colitis (UC). Two authors independently extracted study data and assessed each study’s risk-of-bias. We examined heterogeneity and small-study effect, and calculated summary estimates using random-effects models. Stratified analyses and meta-regression were employed to study the association between study-level characteristics and effect estimates. The strength of epidemiological evidence was assessed through prespecified criteria. Results We synthesized 57 studies examining the smoking-related risk of developing CD and UC. Non-Jewish White smokers were at increased risk of CD (29 studies; RR: 1.95, 95% CI: 1.69‒2.24; moderate evidence). No association was observed in Asian, Jewish and Latin-American populations (11 studies; RR: 0.97; 95% CI: 0.83–1.13), with no evidence of heterogeneity across these ethnicities. Smokers were at reduced risk of UC (51 studies; RR: 0.55, 95% CI: 0.48–0.64; weak evidence) irrespectively of ethnicity; however, cohort studies, large studies and those recently published showed attenuated associations. Conclusions This meta-analysis did not identify any increased risk of CD in smokers in ethnicities other than non-Jewish Whites, and confirmed the protective effect of smoking on UC occurrence. Future research should characterize the genetic background of CD patients across different ethnicities to improve our understanding on the role of smoking in CD pathogenesis.

Leukemia in hospitalized patients with inflammatory bowel disease: An analysis of the National Inpatient Sample (NIS) database.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10576-10576
Author(s):  
Colin Wikholm ◽  
Shiva Shankar Vangimalla ◽  
Ehab Abaza ◽  
Akram Ahmad ◽  
Ioannis Pothoulakis ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Age Groups ◽  
Black Patients ◽  
Increased Risk ◽  
Leukemia Diagnosis ◽  
Inflammatory Bowel ◽  
Over Time ◽  
White Patients

10576 Background: Inflammatory bowel disease (IBD) and use of immunosuppressive therapy in IBD is linked with increased risk of leukemia. We studied the NIS database from 2003-2017 to analyze trends in any type of leukemia in IBD hospitalizations over time and examined the role of age, sex, and race. Methods: We analyzed NIS data of all adult hospitalizations for ulcerative colitis (UC) or Crohn’s disease (CD) with any type of leukemia as a primary or secondary diagnosis using validated ICD 9/10 codes. Age, sex, and racial demographics were collected. Trend analysis of leukemia was performed with Cochran-Armitage and Jonckheere-Terpstra tests. Results: Overall Trends: From 2003-2017, a total of 11,385 of 2,235,413 (0.51%) CD hospitalizations and 8,105 of 1,324,746 (0.61%) UC hospitalizations contained diagnosis of leukemia. An increase in leukemia was seen in both CD and UC group from 0.24% to 0.79% (pTrend < 0.0001) and 0.28% to 0.81% (pTrend < 0.0001) respectively. Sex: In both UC and CD patients, leukemia diagnoses were predominantly male in 2003 but approximated a near 1:1 ratio by 2017 (Table). In CD, the proportion of female (FEM) leukemia diagnoses grew from 31.33% to 45.05% from 2003 to 2017 (pTrend = 0.1898). In UC, the proportion of female leukemia diagnoses grew from 27.49% to 45.79% from 2003 to 2017 (pTrend = 0.0030). Age: Leukemia was more common with increasing age, with no significant changes in proportion of cases between age groups over time (pTrend >.05). Ethnicity: White patients composed 87.80% and 84.24% of leukemia diagnoses in CD and UC, respectively. In CD, an increasing proportion of leukemia diagnoses occurred in black (BK) patients, and a decreasing proportion occurred in white patients (pTrends <.0001; Table 1) during the study time. No trends in race were observed in the UC group (pTrend = 0.4229). Conclusions: Our study showed an increased prevalence of leukemia in CD and UC hospitalizations from 2003-2017 which may be related to increasing use of immunosuppressants such as anti-TNF medications. In both CD and UC, leukemia was male-predominant, but increasingly female by 2017. Rate of leukemia diagnosis increased with age. In the CD group but not the UC group, leukemia was increasingly prevalent in black patients.[Table: see text]

N04 Knowledge, attitude and perception of inflammatory bowel disease patients towards colorectal cancer risk, its management and the role of healthcare providers: a cross-sectional study in the UK

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S659-S659
Author(s):  
F Khan ◽  
W Czuber-Dochan ◽  
C Norton
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
Risk Management ◽  
Cancer Risk ◽  
Bowel Disease ◽  
Initiation Time ◽  
Cross Sectional ◽  
Early Cancer Diagnosis ◽  
Inflammatory Bowel

Abstract Background Inflammatory bowel disease (IBD) increases the risk of colorectal cancer (CRC) and requires specialised cancer risk management. Although literature exists on general disease-related knowledge in IBD patients, limited studies have assessed IBD patients’ knowledge of CRC risk and its management. Consequently, patient perception of the role of a healthcare provider (HCP) in patient education of CRC risk and their attitude towards recommended risk management has not been assessed in UK IBD patients. Methods We conducted a cross-sectional online survey with IBD patients recruited via charity sources from April-July 2019. Adult patients (&gt;18 years) with a confirmed diagnosis of IBD for 2 years and adequate command of English language were included. A self-designed and piloted questionnaire with open and closed-ended questions was used. Closed-ended data were analysed using descriptive statistics and open-ended responses were analysed using content analysis. Fischer’s exact test and bivariate logistic regression were used to test for association between knowledge and patient demographics. Results 92 participants, including 52.5% CD and 67.5% females, responded. 88% knew that IBD increases CRC risk. The mean fear of CRC risk (0–10 visual analogue scale) was 6.37 (SD ± 2.8). One-fifth were aware of colonoscopy as the best screening tool; 88% were unaware of screening initiation time. 90% would agree to their doctor’s recommendation of colonoscopy to ensure early cancer diagnosis and treatment. For dysplasia with 10% risk of CRC, 46.7% would not agree to colectomy mainly due to 10% risk of CRC not being high enough to undergo surgery. Forty-eight per cent of participants said that they never had a discussion about increased CRC risk in IBD with their doctor. Almost two-thirds were not informed about the role of screening/surveillance in cancer. Two-thirds were satisfied with the information provided by their HCP. Overall, patients desired more information about their individualised cancer risk and services available for managing the increased risk. Conclusion IBD patients are well informed about IBD-associated CRC risk, feared this risk greatly but were poorly aware of screening initiation time. HCP’s role in cancer knowledge dissemination was sub-optimal and patients desired more knowledge. We need deeper understanding of patients’ educational needs related to CRC.

Inflammatory bowel disease and colonic disorders

2021 ◽  
pp. 150-208
Author(s):  
Thomas Marjot
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Core Curriculum ◽  
Therapeutic Drug ◽  
Biologic Therapies ◽  
Inflammatory Bowel ◽  
Prevention Of Cancer ◽  
Curriculum Topics

This chapter covers core curriculum topics relating to inflammatory bowel disease (IBD) and colonic disorders. A diagnostic approach to IBD is covered including the role of imaging, endoscopy, histopathology and clinical features. Pathophysiology and epidemiology of IBD is detailed. Management of Ulcerative colitis and Crohn’s disease includes assessment of disease severity, imaging modalities and therapeutic management. Particular focus is given to therapeutic drug monitoring and indications for biologic therapies. Surgical management of IBD is broadly covered including indications, timing and approach. Coverage is also given to the diagnosis and management of extra-intestinal manifestations of IBD, IBD in special situations (pregnancy, elderly, transition) and the prevention of cancer in IBD. Colorectal cancer and benign conditions including constipation, functional gut disorders and other colitides are also featured.

scholarly journals Colorectal Cancer in Inflammatory Bowel Disease

2020 ◽  
Vol 33 (05) ◽  
pp. 305-317
Author(s):  
Martina Nebbia ◽  
Nuha A. Yassin ◽  
Antonino Spinelli
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Severe Disease ◽  
Critical Role ◽  
Mucosal Inflammation ◽  
Surgical Approaches ◽  
Increased Risk ◽  
Significant Difference ◽  
Inflammatory Bowel

AbstractPatients with inflammatory bowel disease (IBD) are at an increased risk for developing colorectal cancer (CRC). However, the incidence has declined over the past 30 years, which is probably attributed to raise awareness, successful CRC surveillance programs and improved control of mucosal inflammation through chemoprevention. The risk factors for IBD-related CRC include more severe disease (as reflected by the extent of disease and the duration of poorly controlled disease), family history of CRC, pseudo polyps, primary sclerosing cholangitis, and male sex. The molecular pathogenesis of inflammatory epithelium might play a critical role in the development of CRC. IBD-related CRC is characterized by fewer rectal tumors, more synchronous and poorly differentiated tumors compared with sporadic cancers. There is no significant difference in sex distribution, stage at presentation, or survival. Surveillance is vital for the detection and subsequently management of dysplasia. Most guidelines recommend initiation of surveillance colonoscopy at 8 to 10 years after IBD diagnosis, followed by subsequent surveillance of 1 to 2 yearly intervals. Traditionally, surveillance colonoscopies with random colonic biopsies were used. However, recent data suggest that high definition and chromoendoscopy are better methods of surveillance by improving sensitivity to previously “invisible” flat dysplastic lesions. Management of dysplasia, timing of surveillance, chemoprevention, and the surgical approaches are all areas that stimulate various discussions. The aim of this review is to provide an up-to-date focus on CRC in IBD, from laboratory to bedside.

Surveillance in inflammatory bowel disease: an overview

2019 ◽  
Vol 17 (8) ◽  
pp. 32-37
Author(s):  
Sara Koo ◽  
Jignesh Jatania ◽  
Colin Rees
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Disease Duration ◽  
The Other ◽  
Surveillance Colonoscopy ◽  
Targeted Biopsy ◽  
White Light Endoscopy ◽  
Increased Risk ◽  
Inflammatory Bowel

Patients with inflammatory bowel disease (IBD), including both ulcerative colitis and Crohn's disease, are at an increased risk of developing colorectal cancer. It is well accepted that this risk increases after 8–10 years of disease duration. Patients should be offered a surveillance colonoscopy after this time. Previously, white-light endoscopy with random biopsies every 10 cm was undertaken for surveillance, but recent evidence suggests that chromoendoscopy along with targeted biopsy is superior to this and the other available methods. This article reviews the available evidence for IBD surveillance, surveillance guidelines and the evidence for chromoendoscopy. Additionally, an overview of the assessment, reporting of any visible abnormal lesions and management of subsequently proven dysplastic lesions is given.

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