The risk of colorectal cancer in patients with Inflammatory Bowel Disease

Patients with inflammatory bowel disease (IBD), which includes Crohn's Disease and Ulcerative Colitis, are at increased risk of developing colorectal cancer (CRC) when compared to the general population. Colorectal cancer associated with long-lasting (more than 8-10 years of diagnosis) bowel inflammation (colitis) is one of the major complications of inflammatory bowel disease. The mechanisms underlying the progression of inflammation to bowel cancer are not fully understood. A team of researchers from i3S, coordinated by Salomé Pinho, described the main mechanisms underlying the development of CRC associated with IBD. In this article, published in Inflammatory Bowel Disease (official journal of the Crohn’s and Colitis Foundation of America), the authors give special attention to the role of glycans (sugar/carbohydrate structures) that line the intestinal mucosa in the deregulation of the interaction between the microbiome and the inflammatory response. This article reviews the most updated scientific evidences supporting the contribution of glycans at the surface of the intestinal mucosa (glycocalyx) in the processes that lead to the progression of chronic inflammation to malignant transformation, opening doors to the identification of new risk biomarkers of CRC, as well as new therapeutic targets in the prevention of CRC in IBD.

Authors and Affiliations:

Eduarda Leite-Gomes^1*; Ana M. Dias^1*; Catarina M. Azevedo¹; Beatriz Santos-Pereira¹; Mariana Magalhães^1,2; Mónica Garrido²; Rita Amorim^1,3,6; Paula Lago²; Ricardo Marcos-Pinto^2,4,5; Salomé S. Pinho^1,4,6

¹ Institute for Research and Innovation in Health (i3S), University of Porto, Porto, Portugal. 

² Department of Gastroenterology, Porto Centre Hospital, Porto, Portugal.

³ Pediatrics Department, Centro Hospitalar e Universitário São João, Porto, Portugal.

⁴ Institute of Biomedical Sciences of Abel Salazar (ICBAS), University of Porto, Porto, Portugal.

⁵ Centre for Research in Health Technologies and Information Systems (CINTESIS), University of Porto, Portugal.

⁶ Medical Faculty, University of Porto, Porto, Portugal.

^* Contributed equally

Abstract:

Colitis-associated cancer is a major complication of inflammatory bowel disease remaining an important clinical challenge in terms of diagnosis, screening, and prognosis. Inflammation is a driving factor both in inflammatory bowel disease and cancer, but the mechanism underlying the transition from colon inflammation to cancer remains to be defined. Dysregulation of mucosal glycosylation has been described as a key regulatory mechanism associated both with colon inflammation and colorectal cancer development. In this review, we discuss the major molecular mechanisms of colitis-associated cancer pathogenesis, highlighting the role of glycans expressed at gut epithelial cells, at lamina propria T cells, and in serum proteins in the regulation of intestinal inflammation and its progression to colon cancer, further discussing its potential clinical and therapeutic applications.

Journal: Inflammatory Bowel Diseases

Link: https://academic.oup.com/ibdjournal/advance-article/doi/10.1093/ibd/izab291/6446097?login=true