ULCERATIVE COLITIS FROM GENETICS TO COMPLICATIONS Edited by Mustafa M. Shennak Ulcerative Colitis from Genetics to Complications Edited by Mustafa M. Shennak Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2011 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. As for readers, this license allows users to download, copy and build upon published chapters even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. Notice Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published chapters. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book. Publishing Process Manager Danijela Duric Technical Editor Teodora Smiljanic Cover Designer InTech Design Team First published January, 2012 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechweb.org Ulcerative Colitis from Genetics to Complications, Edited by Mustafa M. Shennak p. cm. ISBN 978-953-307-853-3 Contents Preface IX Chapter 1 Evolutionary Insights into the “Population-Specificity” of the Genetic Factors Associated with Inflammatory Bowel Diseases 1 Shigeki Nakagome and Hiroki Oota Chapter 2 Research of Immunology Markers of UC 21 David Díaz-Jiménez, Katya Carrillo, Rodrigo Quera and Marcela A. Hermoso Chapter 3 Ulcerative Colitis and Microorganisms 41 José Miguel Sahuquillo Arce and Agustín Iranzo Tatay Chapter 4 Primary Sclerosing Cholangitis and Ulcerative Colitis 63 Sophia Jagroop and Ramona Rajapakse Chapter 5 Colorectal Cancer in Ulcerative Colitis Patients 77 Joseph D. Feuerstein and Sharmeel K. Wasan Chapter 6 Ulcerative Colitis and Colorectal Cancer: Aneuploidy and Implications for Improved Screening 111 Jens K. Habermann, Gert Auer, Thomas Ried and Uwe J. Roblick Chapter 7 Carcinogenesis in Ulcerative Colitis 127 Adam Humphries, Noor Jawad, Ana Ignjatovic, James East and Simon Leedham Chapter 8 Ulcerative Colitis-Associated Colorectal Cancer Prevention by 5-Aminosalicylates: Current Status and Perspectives 149 Jean-Marie Reimund, Marion Tavernier, Stéphanie Viennot, Inaya Abdallah Hajj Hussein, Benoît Dupont, Anne-Marie Justum, Abdo R. Jurjus, Jean-Noël Freund and Mathilde Lechevrel VI Contents Chapter 9 Ulcerative Colitis 167 Yousef Ajlouni and Mustafa M. Shennak Chapter 10 Current and Novel Treatments for Ulcerative Colitis 189 Cuong D. Tran, Rosa Katsikeros and Suzanne M. Abimosleh Preface Ulcerative Colitis (UC) is a rapidly evolving medical field and will continue to be very exiting for the foreseable future. Although the underlaying cause of this disease is still unknown, great scientific research dealing with various issues related to different aspects of this disease are published every day. Chapters included in this book review the most recent literature on related advancements on this chronic, controllable yet incurable disease. Aspects like epidemiology, pathophysiology, genetics, incriminated etiologies, clinical aspects, complications, disease management including advancements in the diagnostic and therapeutic options, have been documented within this book by well known clinicians, researchers and world-wide authorities in their fields. Subjects that have been tackled in this book include: Evolutionary Insights into the “Population-Specificity” of the Genetic Factors Associated with Inflammatory Bowel Diseases by Dr Shigeki Nakagome and Hiroki Oota Research of Immunology Markers of UC by Dr. David Díaz-Jiménez, Dr Katya Carrillo, Dr Rodrigo Quera and Dr Marcela A. Hermoso Ulcerative Colitis and Microorganisms by Dr. José Miguel Sahuquillo Arce and Dr Agustín Iranzo Tatay Primary Sclerosing Cholangitis by Dr Sophia Jagroop and Prof. Ramona Rajapakse Colorectal Cancer in Ulcerative Colitis Patients by Dr Joseph D. Feuerstein and Dr Sharmeel K. Wasan Ulcerative Colitis and Colorectal Cancer: Aneuploidy and Implications for Improved Screening by Dr Jens K. Habermann, Dr Gert Auer, Dr Thomas Ried and Dr Uwe J. Roblick Carcinogenesis in Ulcerative Colitis by Dr Adam Humphries, Dr Noor Jawad, Dr Ana Ignjatovic, Dr James East and Dr. Simon Leedham X Preface Ulcerative Colitis-Associated Colorectal Cancer Prevention by 5-Aminosalicylates: Current Status and Perspectives by Dr Jean-Marie Reimund et al. Drug therapy for UC by Dr. Yousef Ajlouni and Prof. Mustafa Shennak. Novel treatments for Ulcerative Colitis by Dr Tran Cuong, Dr. Rosa Katsikeros, Dr Suzanne M. Abimosleh All authors have done a great job documenting the most up to date literature on each subject. I am confident that this book on UC will be a valuable addition to each doctor’s library interested in this subject or for physicians dealing with patients suffering from this disease. Authors have also included figures and diagrams to depict their point and to reach easily to the minds of the readers in the simplest way. Mustafa M. Shennak Faculty of Medicine, University of Jordan, Jordan [...]... immunological markers for UC 22 Ulcerative Colitis from Genetics to Complications 2 Intestinal inflammatory process in ulcerative colitis IBD is a chronic, relapsing-remitting condition that affects the gastrointestinal tract The aetiology of IBD has not been fully elucidated, although, it has been described as a multifactorial disease, in which genetics, environmental factors and immune system have a... (0.347 - 1.568) 0.737 (0.608 - 3.693) 1.499 (0.448 - 1.322) 0.770 UC 10 Ulcerative Colitis from Genetics to Complications Table 3 Associations of alleles and genotypes with Crohn’s disease or ulcerative colitis in the Kyushu subjects Evolutionary Insights into the “Population-Specificity” of the Genetic Factors Associated with Inflammatory Bowel Diseases 11 2.3.3 Differences in the Genotype Relative Risk... 0.063 0.146 - b LRT p -values Evolutionary Insights into the “Population-Specificity” of the Genetic Factors Associated with Inflammatory Bowel Diseases 13 Table 4 Modified genotype relative risk (mGRR) test of rs3810936 for CD and UC in the Kyushu subjects 14 Ulcerative Colitis from Genetics to Complications 2.3.4 Population-specific susceptibility to IBD Given that CD and UC inheritance do not follow... inflammatory response that will be detected by specialized sensors or sentinel cells This process will subsequently lead to the production of inflammatory mediators that will affect different tissues; eliciting changes in their functional state that will optimize an adaptation process to the harmful condition associated to the inflammatory response (Medzhitov, 2010) Due to the chronicity of the inflammatory... consequences of population-specific susceptibility to IBD and the importance of its use for diverse human populations in the future of GWAS 2 Ulcerative Colitis from Genetics to Complications 2 Genetic studies of IBD and population-specific susceptibility IBDs are complex diseases in which multiple genetic and environmental factors are likely to contribute to pathogenesis Human genomics studies have concentrated... explaining a compensatory mechanism to restrain the exaggerated inflammation triggered by over-activation of TLR2 in intestinal mucosa of UC patients This inflammatory condition might explain the 24 Ulcerative Colitis from Genetics to Complications participation of sTLR2 to counteract the epithelial damage generated as a consequence of activation of pro-inflammatory signalling pathways, without restabilising... alleles – including common alleles and populationspecific alleles – appeared before human population divergences 4 Ulcerative Colitis from Genetics to Complications history (Fig 1b) However, this equilibrium model is not applied to complex diseases, because of incomplete penetrance, gene -to- environmental interactions and polygenic inheritance Most of the complex disease alleles spread across human populations,... 23/77 100/0 0/100 0/100 0/100 A /a UC Allele frequency Controls 68/32 63/38 0/100 63/37 26/74 100/0 0/100 0/100 0/100 A /a 8 Ulcerative Colitis from Genetics to Complications Evolutionary Insights into the “Population-Specificity” of the Genetic Factors Associated with Inflammatory Bowel Diseases 9 susceptibility genes identified in Europeans are not significantly associated with CD in the Japanese... gives rise to disease phenotypes The genetic variants that have been found to confer IBD risks point to the importance of innate immunity, autophagy and phagocytosis in IBD pathogenesis Hence, we attribute population-specific IBD susceptibility to natural selection on the IBD variants, Evolutionary Insights into the “Population-Specificity” of the Genetic Factors Associated with Inflammatory Bowel... et al 2008 Loci on 20q13 and 21q22 are associated with pediatric-onset inflammatory bowel disease Nat Genet 40:1211-1215 18 Ulcerative Colitis from Genetics to Complications Libioulle, C., E Louis, S Hansoul, C Sandor, F Farnir, D Franchimont et al 2007 Novel Crohn disease locus identified by genome-wide association maps to a gene desert on 5p13.1 and modulates expression of PTGER4 PLoS Genet 3:e58 . ULCERATIVE COLITIS FROM GENETICS TO COMPLICATIONS Edited by Mustafa M. Shennak Ulcerative Colitis from Genetics to Complications Edited by. divergences Ulcerative Colitis from Genetics to Complications 4 history (Fig. 1b). However, this equilibrium model is not applied to complex diseases, because of incomplete penetrance, gene -to- environmental. Insights into the “Population-Specificity” of the Genetic Factors Associated with Inflammatory Bowel Diseases 7 Table 1. Susceptibility genes of IBD Ulcerative Colitis from Genetics to Complications