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Expert Review of Molecular Diagnostics Volume 6, 2006 - Issue 3
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Review

Role of genes, the environment and their interactions in the etiology of inflammatory bowel diseases

Farid E Ahmed Clinical Professor, The Brody School of Medicine at East Carolina University, Department of Radiation Oncology, Leo W Jenkins Cancer Center, Greenville, NC 27858, USA. [email protected]
Pages 345-363 | Published online: 09 Jan 2014

References

  • Wilks S, Morton W.Lectures on Pathological Anatomy, 2nd Ed. Lindsay and Blakiston, PA, USA, 408–409 (1875).
  • Lockhart-Mummery JP. Discussion on ulcerative colitis.Proc. R. Soc. Med.2, 92 (1909).
  • Crohn BB , Ginzburgh L, Oppenheimer GD. Regional ileitis: a pathologic and clinical entity.J. Am. Med. Assoc.99, 1323–1329 (1932).
  • Cummings JRF, Jewell DP. Clinical implications of inflammatory bowel diseases: genetics or phenotype.Inflamm. Bowel Dis.11, 56–61 (2005).
  • Rhodes JM, Campbell BJ. Inflammation and colorectal cancer. IBD-associated and sporadic cancer compared.Trends Mol. Med.6, 10–16 (2002).
  • Bonen DK, Cho JH. The genetics of inflammatory bowel disease.Gastroenterology124, 521–536 (2003).
  • Ahmad T, Tamboli CP, Jewell D et al. Clinical relevance of advances in genetics and pharmacogenetics of IBD.Gastroenterology126, 1533–1549 (2004).
  • Satsungi J, Marecroft J, Shah NB et al. Genetics of inflammatory bowel disease: scientific and clinical implications.Best Pract. Res. Clin. Gastroenterol.17, 3–18 (2003).
  • Kurata JH, Kantor-Fish S, Frankl H et al. Crohn’s disease among ethnic groups in a large health maintenance organization.Gastroenterology102, 1940–1948 (1992).
  • Ogunbi SO, Ransom JA, Sullivan K et al. Inflammatory bowel disease in African–American children living in Georgia.J. Pediatr.133, 103–107 (1998).
  • Yang H, Taylor KD, Rotter JI. Inflammatory bowel disease. I. Genetic epidemiology.Mol. Genet. Metab.74, 1–21 (2001).
  • Yang H, McElree C, Roth MP et al. Familial empirical risks for inflammatory bowel disease: differences between Jews and non-Jews.Gut34, 517–524 (1993).
  • Binder V. Genetic epidemiology of inflammatory bowel disease.Dig. Dis.16, 351–355 (1998).
  • Brant SR, Panhuysen CI, Bailey-Wilson JE et al. Linkage heterogeneity for the IBD1 locus in Crohn’s disease pedigrees by disease onset and severity.Gastroenterology118, 1483–1490 (2000).
  • Rioux JD, Daly MJ, Silverberg MS et al. Genetic variation in the 5q31 ctokine gene cluster confers susceptibility to Crohn disease.Nature Genet.29, 223–228 (2001).
  • Fisher SA, Hampe J, Macpherson AJ et al. Sex stratification of an inflammatory bowel disease genome search shows male-specific linkage to the HLA region of chromosome 6.Eur. J. Hum. Genet.10, 259–165 (2002).
  • Peters M, Cortot A, Vermeire S et al. Familial and sporadic inflammatory bowel disease: different entities?Inflamm. Bowel Dis.6, 314–320 (2000).
  • Lee JC, Lennard-Jones JE. Inflammatory bowel disease in 67 families each with three or more affected first-degree relatives.Gastroenterology111, 587–596 (1996).
  • Petronis A, Petroniene R. Epigenetics of inflammatory bowel disease.Gut47, 302–306 (2000).
  • Subhani J, Montgomery SM, Pounder RE et al. Concordance rates of twins and siblings in inflammatory bowel disease.Gut42, A40 (1998).
  • Ahmed FE. Gene–gene, gene–environment and multiple interactions in colorectal cancer.J. Env. Sci. Health C24,1–101 (2006).
  • Hugot JP, Laurent-Puig P, Gower-Rousseau C et al. Mapping of susceptibility locus for Crohn’s disease on chromosoma 16.Nature379, 821–823 (1996).
  • Zheng CQ, Hu GZ, Zeng ZS et al. Progress in searching for susceptibility gene for inflammatory bowel disease by positional cloning.World J. Gastroenterol.9, 1646–1656 (2003).
  • Hugot JP, Chamaillard M, Zouali H et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease.Nature411, 599–603 (2001).
  • Ogura Y, Bonen DK, Inohara N et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease.Nature411, 603–606 (2001).
  • Hampe J, Cuthbert A, Croucher PJ et al. Association between insertion mutation in NOD2 gene and Crohn’s disease in German and British populations.Lancet357, 1925–1928 (2001).
  • Franchimont D, Vermeire S, El Housni H et al. Deficient host–bacteria interactions in inflammatory bowel disease? The toll-like receptor (TLR)-4 Asp299Gly polymorphism is associated with Crohn’s disease and ulcerative colitis.Gut53, 987–992 (2004).
  • Torok HP, Glas J, Tonenchi L et al. Polymorphism of the lipopolysaccharide-signaling complex in inflammatory bowel disease: association of a mutation in the Toll-like receptor 4 gene with ulcerative colitis.Clin. Immunol.112, 85–91 (2004).
  • Arnott IDR, Nimmo ER, Drummond HE et al. NOD2/CAD15, TLR4 and CD14 mutations in Scottish and Irsh Crohn’s disease patients: evidence for genetic heterogeneity within Europe?Genes Immun.5, 417–425 (2004).
  • Lesage S, Zouali H, Cezard JP et al. CARD15/NOD2 mutational analysis and genotype–phenotype correlation in 612 patients with inflammatory bowel disease.Am. J. Hum. Genet.70, 845–857 (2002).
  • Ahmad T, Armuzzi A, Bunce M et al. The molecular classification of the clinical manifestations of Crohn’s disease.Gastroenterology122, 854–866 (2002).
  • Cuthbert AP, Fisher SA, Mirza MM et al. The contribution of NOD2 gene mutation to the risk and site of disease in inflammatory bowel disease.Gastroenterology122, 867–874 (2002).
  • Abreu MT, Taylor KD, Lin YC et al. Mutations in NOD2 are associated with fibrostenosing disease in patients with Crohn’s disease.Gastroenterology123, 679–688 (2002).
  • Linde K, Boor PP, Houwing-Duistermaat JJ et al. CARD15 and Crohn’s disease: healthy homozygous carriers of the 3020insC frameshift mutation.Am. J. Gastroenterol.98, 613–617 (2003).
  • Zhou Z, Lin XY, Akolkar PN et al. Variation at NOD2/CARD15 in familial and sporadic cases of Crohn’s disease in the Ashkenazi Jewish population.Am. J. Gastroenterol.97, 3095–3101 (2002).
  • Sugimura K, Taylor KD, Lin YC et al. A novel NOD2/CARD15 haplotype conferring risk for Crohn disease in Ashkenazi Jews.Am. J. Hum. Genet.72, 509–518 (2003).
  • Andruilli A, Annese V, Latiano A et al. The frame-shift mutation of the NOD2/CARD15 gene is significantly increased in ulcerative colitis: an *IG-IBD study.Gastroenterology126, 625–627 (2004).
  • Heel DA, Ghosh S, Butler M. Muramyl dipeptide and toll-like receptor sensitivity in NOD2-associated Crohn’s disease.Lancet365, 1794–1796 (2005).
  • Buhner S, Buning C, Genschel J et al. Genetic basis for increased intestinal permeability in families with Crohn’s disease: role of CARD15 3020insC mutation.Gut55, 342–347 (2006).
  • Esters N, Pierik M, van Steen K et al. Transmission of CARD15(NOD2) variants with families of patients with inflammatory bowel disease.Am. J. Gastroenterol.99(2), 299–305 (2004).
  • McGovern DP, Hysi P, Ahmad T et al. Association between a complex insertion/deletion polymorphism in NOD1(CARD4) and susceptibility to inflammatory bowel disease.Hum. Mol. Genet.14, 1245–1250 (2005).
  • Satsangi J, Parkes M, Louis E et al. Two stage genome-wide search in inflammatory bowel disease provides evidence for susceptibility loci on chromosomes 3, 7 and 12.Nature Genet.14, 199–202 (1996).
  • Yang H, Plevy SE, Taylor K et al. Linkage of Crohn’s disease to the major histocompatability complex region is detected by multiple nonparametric analyses.Gut44, 519–526 (1999).
  • Stokkers PC, Reitsma PH, Tytgat GN et al. HLA-DR and -DQ phenotypes in inflammatory bowel disease: a meta-analysis.Gut45, 395–401 (1999).
  • Ahmad T, Armuzzi A, Neville M et al. The contribution of human leucocyte antigen complex genes to disease phenotype in ulcerative colitis.Tissue Antigens62, 527–535 (2003).
  • Armuzzi A, Ahmad T, Ling KL et al. Genotype–phenotype analysis of the Crohn’s disease susceptibility haplotype on chromosome 5q31.Gut52, 1133–1139 (2003).
  • Peltekova VD, Wintle RF, Rubin LA et al. Functional variants of OCTN cation transporter genes are associated with Crohn disease.Nature Genet.36, 471–475 (2004).
  • Vermeire S. DLG5 and OCTN. Two gold medals for the genetics of inflammatory bowel disease.Inflamm. Bowel Dis.10, 888–890 (2004).
  • Stoll M, Corneliussen B, Costello CM et al. Genetic variation in DLG5 is associated with inflammatory bowel disease.Nature Genet.36, 476–480 (2004).
  • Low JH, Williams FA, Yang X et al. Inflammatory bowel disease is linked to 19p13 and associated with ICAM-1.Inflamm. Bowel Dis.10, 173–181 (2004).
  • Braun C, Zahn R, Martin K et al. Polymorphisms of the ICAM-1 gene are associated with inflammatory bowel diseases regardless of the p-ANCA status.Clin. Immunol.101, 357–360 (2001).
  • Pierik M, Yang H, Barmada MM et al. The IBD international genetics consortium provides further evidence for linkage to IBD4 and shows gene–environment interaction.Inflamm. Bowel Dis.11, 1–7 (2005).
  • Mahmud N, Molloy A, McPanthin J et al. Increased prevalence of methylenetetrahydrofolate reductase C677T variant in patients with inflammatory bowel disease, and its clinical implications.Gut45, 389–394 (1995).
  • Duncan H, Swan C, Green J et al. Susceptibility to ulcerative colitis and Crohn’s disease: interactions between glutathione S-transferase GSTM1 and GSTT1 genotype.Clin. Chim. Acta240, 53–61 (1995).
  • Chinetti G, Fruchart JC, Staels B. Peroxisomeproliferator-activated receptors (PARs): nuclear receptors at the crossroads between lipid metabolism and inflammation.Inflamm. Res.49, 497–505 (2000).
  • Potocnik U, Ferkolj I, Glavac D et al. Polymorphism in multidrug resistance 1 (MDR1) gene are associated with refractory Crohn disease and ulcerative colitis.Genes Immun.5, 530–539 (2004).
  • Aithal GP, Craggs A, Day CP et al. Role of polymorphism in the interleukin-10 gene in determining disease susceptibility and phenotype in inflammatory bowel disease.Dig. Dis. Sci.46, 1520–1525 (2001).
  • Owens DW, Wilson NJ, Hill AJM et al. Human keratin 8 mutations that disrupt filament assembly observed in inflammatory bowel disease.J. Cell Sci.117, 1989–1999 (2004).
  • Aithal GP, Day CP, Leathart J et al. Association of single nucleotide polymorphism in the interleukin-4 gene and interleukin-4 receptor gene with Crohn’s disease in a British population.Genes Immun.2, 44–47 (2001).
  • Bagnoli S, Putignano AL, Melean G et al. Susceptibility to refractory ulcerative colitis is associated with polymorphism in the hMLH1 mismatch repair gene.Inflamm. Bowel Dis.10, 705–708 (2004).
  • Klein W, Tromm A, Griga T et al. Polymorphism in IL11 gene is associated wth ulcerative colitis.Genes Immun.3, 494–496 (2002).
  • Balding J, Livingstone WJ, Conroy J et al. Inflammatory bowel disease: the role of inflammatory cytokine gene polymorphism.Mediators Inflamm.13, 181–187 (2004).
  • Karban AS, Okazaki T, Panhuysen F et al. Functional annotation for novel NFκB1 promoter polymorphism that increases risk for ulcerative colitis.Mol. Genet.13, 35–45 (2004).
  • Hussain SP, Amstad P, Raja K et al. Increased p53 mutation load in noncancerous colon tissue from ulcerative colitis: a cancer-prone chronic inflammatory disease.Cancer Res.60, 3333–3337 (2000).
  • Klein W, Tromm A, Griga T et al. A polymorphism in the CD-14 gene is associated wth Crohn’s disease.Scand. J. Gastroenterol.3, 494–496 (2002).
  • Polak RD, Ackerman Z, Eliakim R et al. The BsmI vitamin D receptor gene polymorphism is associated with ulcerative colitis in Jewish Ashkenzai patients.Genetic Test.8, 1–4 (2004).
  • Dieckgraefe BK, Stenson WI, Korzenik JR. Analysis of mucosal gene expression in inflammatory bowel disease by parallel oligonucleotide arrays.Phys. Genomics4, 1–11 (2000).
  • Uthoff SMS, Eichenberger MR, Lewis RK et al. Identification of candidate genes in ulcerative colitis and Crohn’s disease using cDNA array technology.Int. J. Oncol.19, 803–816 (2001).
  • Lawrence IC, Fiocchi C, Chakravarti S. Ulcerative colitis and Crohn’s disease: distinctive gene expression profiles and normal susceptibility candidate genes.Hum. Molec. Genet.10, 445–456 (2001).
  • Dooley TP, Curto EV, Reddy SP et al. Regulation of gene expression in inflammatory bowel disease and correlation with IBD drugs.Inflamm. Bowel Dis.10, 1–14 (2004).
  • Negoro K, McGovern DP, Kinouchi Y et al. Analysis of the IBD5 locus and potential gene–gene interactions in Crohn’s disease.Gut52, 541–546 (2003).
  • Farmer MA, Sundberg JP, Bristol U et al. A major quantitative trait locus on chromosome 3 controls colitis severity in IL-10-deficient mice.Proc. Natl Acad. Sci. USA98, 13820–13825 (2001).
  • Cho JH, Nicolae DL, Gold LH et al. Identification of novel susceptibility loci for inflammatory bowel disease on chromosome 1p, 3q and 4q: evidence for epistasis between 1p and IBD1.Proc. Natl Acad. Sci. USA95, 7502–7507 (1998).
  • Mirza MM, Fisher SA, King K et al. Genetic evidence for interaction of the 5q31 cytokine locus and the CARD15 gene in Crohn disease.Am J. Hum. Genet.72, 1018–1022 (203).
  • Giallourakis C, Stoll M, Miller K et al. IBD5 is a general risk factor for inflammatory bowel disease: replication of association with Crohn disease and identification of a novel association with ulcerative colitis.Am. J. Hum. Genet.73, 205–211 (2003).
  • McGovern DPB, van Heel DA, Negoro K et al. Further evidence of IBD5/CARD15(NOD2) epistasis in the susceptibility to ulcerative colitis.Am J. Hum. Genet.73, 1465–1466 (2003).
  • Bonen DK, Ogura Y, Nicolae DL et al. Crohn’s disease-associated NOD2 variants share a significant defect in response to lipopolysaccharide and peptidoglycan.Gastroenterology124, 140–146 (2003).
  • Loftus EV Jr. Clinical epidemiology of inflammatory bowel disease: incidence, prevalence and environmental influence.Gastroenterology126, 1504–1517 (2004).
  • Timmer A. Environmental influence on inflammatory bowel disease manifestations.Digest. Dis.21, 91–104 (2003).
  • Danese S, Sans M, Fiocchi C. Inflammatory bowel disease: the role of environmental factors.Autoimmun. Res.3, 394–400 (2004).
  • Cashma KD, Shanahan F. Is nutrition an etiological factor for inflammatory bowel disease?Eur. J. Gastroenterol. Hepatol.16, 607–613 (2003).
  • Yang SK, Loftus EV Jr, Sandborn WJ. Epidemiology of inflammatory bowel disease in Asia.Inflamm. Bowel Dis.7, 260–270 (2001).
  • Klement E, Cohen RV, Boxman J et al. Breastfeeding and risk of inflammatory bowel disease: a systematic review with meta-analysis.Am. J. Clin. Nutr.80, 1342–1352 (2004).
  • Baron S, Turck D, Leplat C et al. Environmental risk factors in pediatric inflammatory bowel disease: a population-based case–control study.Gut54, 357–363 (2005).
  • Montgomery SM, Lambe M, Wakefield AJ et al. Siblings and the risk of inflammatory bowel disease.Scand. J. Gastroenterol.37, 1301–1308 (2002).
  • Hampe J, Heymann K, Krawczak M, Schreiber S. Association of inflammatory bowel disease with indicators for childhood antigen and infection exposure.Int. J. Colorect. Dis.18(5), 413–417 (2003).
  • Koutroubakis IE, Vlachonikolis IG, Kouroumalis EA. Role of appendicitis and appendectomy in the pathogenesis of ulcerative colitis: a critical review.Inflamm. Bowel Dis.8, 277–286 (2002).
  • Berg DJ, Zhang J, Weinstock JV et al. Rapid development of colitis in NSAID-treated IL-10-deficient mice.Gastroenterology123, 1527–1542 (2002).
  • Alstead EM. The pill: safe sex and Crohn’s disease?Gut45, 165–166 (1999).
  • Calkins BM. A meta-analysis of the role of smoking in inflammatory bowel disease.Dig. Dis. Sci.34, 1841–1854 (1989).
  • Corrao G, Tragnone A, Caprilli R et al. Risk of inflammatory bowel disease attributable to smoking, oral contraception and breastfeeding in Italy: a nationwide case–control study.Int. J. Epidemiol.27, 397–404 (1998).
  • Regueiro M, Kip KE, Heguzi RA. Cigarette smoking and age at diagnoses of inflammatory bowel disease.Inflamm. Bowel Dis.11, 42–47 (2005).
  • Reif S, Lavy A, Keter D et al. Lack of association between smoking and Crohn’s disease but the usual association with ulcerative colitis in Jewish patients in Israel: a multicenter study.Am. J. Gastroenterol.95, 474–478 (2000).
  • Picco MF, Bayless TM. Tobacco consumption and disease duration are associated with fistulizing and structuring behaviors in the first 8 years of Crohn’s disease.Am. J. Gastroenterol.98, 363–368 (2003).
  • Cosnes J, Beaugerie L, Carbonnel F et al. Smoking cessation and the course of Crohn’s disease: an intervention study.Gastroenterology120, 1093–1099 (2001).
  • Birrenbach T, Bocker U. Inflammatory bowel disease and smoking. A review of epidemiology, pathophysiology, and therapeutic implications.Inflamm. Bowel Dis.10, 848–859 (2004).
  • Rachmilewitz D. On smoking, rats, and inflammatory bowel disease.Gastroenterology117, 1008–1011 (1999).
  • Brant SR, Picco MF, Achkar JP et al. Defining complex contributions of NOD2/CARD15 gene mutation and age at onset, and tobacco use in Crohn’s disease phenotypes.Inflamm. Bowel Dis.9, 281–289 (2003).
  • Martini GA, Brandes JW. Increased consumption of refined carbohydrates in patients with Crohn’s disease.Klin. Wochenschr.54, 367–371 (1976).
  • Reif S, Klein I, Lubin F et al. Pre-illness dietary factors in inflammatory bowel disease.Gut40, 754–760 (1997).
  • Greeling BJ, Dagnelie PC, Badart-Smook A et al. Diet as a risk factor for the development of ulcerative colitis.Gastroenterology95, 1008–1013 (2000).
  • Russel MGVM, Engels LG, Muris JW et al. “Modern life” in the epidemiology of inflammatory bowel disease: a case–control study with special emphasis on nutritional factors.Eur. J. Gastroenterol. Hepatol.10, 243–249 (1998).
  • Jowett SL, Seal CJ, Pearce MS et al. Influence of dietary factors on the clinical course of ulcerative colitis: a prospective cohort study.Gut53, 1479–1484 (2004).
  • Tilg H, Kaser A. Diet and relapsing ulcerative colitis: take off the meat?Gut53, 1419–1421 (2004).
  • Camuesco D, Gálvez J, Nieto A et al. Dietary olive oil supplementation with fish oil, rich in EPA and DHA (n-3) polyunsaturated fatty acids, attenuates colonic inflammation in rats with DSS-induced colitis.J. Nutr.135, 687–694 (2005).
  • Seril DN, Liao J, Yang CS et al. Systemic iron supplementation replenishes iron stores without enhancing color carcinogenesis in murine models of ulcerative colitis: comparison with iron-enriched diet.Dig. Dis. Sci.50, 696–707 (2005).
  • Gasche C, Lomer MCE, Gavill I et al. Iron, anemia, and inflammatory bowel disease.Gut53, 1190–1197 (2004).
  • Sakamoto N, Kono S, Wakai K et al. Dietary risk factors for inflammatory bowel disease.Inflamm. Bowel Dis.11, 154–163 (2005).
  • Cantorna MT, Mahon BD. Mounting evidence for vitamin D as an environmental factor affecting autoimmune disease prevalence.Exp. Biol. Med.229, 1136–1142 (2004).
  • Lomer MCE, Hutchinson C, Volkert S et al. Dietary souces of inorganic microparticles and their intake in healthy subjects with Crohn’s disease.Br. J. Nutr.92, 947–955 (2004).
  • Danese S, Sgambato A, Papa A et al. Homocysteine triggers mucosal microvascular activation in inflammatory bowel disease.Am. J. Gastroenterol.100, 886–895 (2005).
  • Nayar M, Rhodes JM. Management of inflammatory bowel disease.Postgrad. Med. J.80, 206–213 (2004).
  • Shanahan F. Probiotics in inflammatory bowel disease – therapeutic rationale and role.Adv. Drug Deliv. Rev.56, 809–818 (2004).
  • Ghosh S, van Heel D, Playford RJ. Probiotics in inflammatory bowel disease: is it all gut flora modulation?Gut53, 620–622 (2004).
  • Ott SJ, Musfeldt M, Wenderoth DF et al. Reduction in diversity of the colonic mucosa associated bacterial microflora in patients with active inflammatory bowel disease.Gut53, 685–693 (2004).
  • Manichanh C, Rigottier-Gois L, Bonnaud E et al. Reduced diversity of faecal microbiota in Crohn’s disease reduced by a metagenomic approach.Gut55, 205–211 (2006).
  • Hamilton-Miller JMT. A review of clinical trials of probiotics in the management of inflammatory bowel disease.Infect. Dis. Rev.3, 83–87 (2001).
  • Rembacken BJ, Snelling AM, Hawkey PM et al. Non-pathogenic Escherichia coli versus mesalazine for the treatment of ulcerative colitis: a randomized trial.Lancet354, 635–639 (1999).
  • Gionchetti P, Rizzello F, Helwig U et al. Prophylaxis of pouchitis onset with probiotic therapy: a double-blind, placebo-controlled trial.Gastroenterology124, 1202–1209 (2003).
  • Neish AS, Gewirtz AT, Zeng H et al. Prokaryotic regulation of epithelial responses by inhibition of IκB-α ubiquitination.Science289, 1560–1563 (2000).
  • Andersen L, Jørgensen VL, Perner A et al. Activation of nuclear factor κB in colonic mucosa from patients with collagenous and ulcerative colitis.Gut54, 503–509 (2005).
  • Cross RK, Wilson KT. Nitric oxide in inflammatory bowel disease.Inflamm. Bowel Dis.9, 179–189 (2003).
  • Chamaillard M, Philpott D, Girardin SE et al. Gene environment interaction mediated by allelic heterogeneity in inflammatory bowel disease.Proc. Natl Acad. Sci. USA100, 3455–3460 (2003).
  • Amre DK, Seidman EG. Etiopathogenesis of pediatric Crohn’s disease. Biologic pathways based on interactions between genetic and environmental factors.Med. Hypotheses60, 344–350 (2003).
  • Amre DK, Seidman EG. DNA variants in cytokine and NOD2 genes, exposures to infections and risk for Crohn’s disease.Paediatr. Perinat. Epidemiol.17, 302–312 (2003).
  • Mizoguchi A, Mizoguchi E, Bhan AR. Immune networks in animal models of inflammatory bowel disease.Inflamm. Bowel Dis.9, 246–259 (2003).
  • Boivin GP, Washington K, Yan K et al. Pathology of mouse models of intestinal cancer: consensus report and recommendations.Gastroenterology124, 762–777 (2003).

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