Environmental factors in the epidemiology of inflammatory bowel disease

Crohn's Disease and Ulcerative Colitis: From Epidemiology and Immunobiology to a Rational Diagnostic and Therapeutic Approach

Volumn , Issue , 2012, Pages 17-38

  Vatn, Morten H ^a,b  

^a OSLO UNIVERSITY HOSPITAL   (Norway)

^b UNIVERSITY OF OSLO   (Norway)

Author keywords

Environment; Geography; Microbiology; Nutrition; Pharmacology; Risk factors; Smoking; Socioeconomy

Indexed keywords

EID: 84899961675     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-1-4614-0998-4_2     Document Type: Chapter

References (124)

1. Munkholm P, Langholz E, Nielsen OH, et al. Incidence and prevalence of Crohn’s disease in the county of Copenhagen, 1962-87: A sixfold increase in incidence. Scand J Gastroenterol. 1992;27:609-14.
2. Lofthus EV. Clinical epidemiology of inflammatory bowel disease: incidence, prevalence, and environmental influences. Gastroenterology. 2004;126:1504-17.
3. Duggan AE, Usmani I, Neal KR, Logan RFA. Appendicectomy, childhood hygiene, Helicobacter pylori status, and risk of inflammatory bowel disease: A case control study. Gut. 1998;43:494-8.
4. Lennard-Jones JE. Classification of inflammatory bowel disease. Scand J Gastroenterol. 1989;24 Suppl 170:2-6.
5. Logan RFA. Inflammatory bowel disease incidence: up, down or unchanged? Gut. 1998;42:309-11.
6. Sonnenberg A, McCarty DJ, Jacobsen SJ. Geographic variation in the incidence of and mortality from inflammatory bowel disease. Dis Colon Rectum. 1986;29:854-61.
7. Primatesta P, Goldacre MJ. Crohn’s disease and ulcerative colitis in England and the Oxford Record linkeage study area: A profile of hospitalized morbidity. Int J Epidemiol. 1995;24:922-8.
8. Cosnes J, Cattan S, Blain A, et al. Long-term evolution of disease behavior of Crohn’s disease. Inflamm Bowel Dis. 2002;8:244-50.
9. Vind I, Riis L, Knudsen E, et al. Increasing incidences of inflammatory bowel disease and decreasing surgery rates in Copenhagen city and county, 2003-2005: A population based study from the Danish Crohn colitis database. Am J Gastroenterol. 2006;101:1274-82.
10. Shivananda S, Lennard-Jones J, Logan RFA, et al. Incidence of Inflammatory bowel disease across Europe: Is there a difference between north and south? Results of the European collaborative study on inflammatory bowel disease(EC-IBD). Gut. 1996;39:690-7.
11. Moum B, Vatn MH, Ekbom A, et al. Incidence of ulcerative colitis and indeterminate colitis in four counties of south-eastern Norway 1990-1993. A large prospective population-based study. Scand J Gastroenterol. 1996;31:356-60.
12. Moum B, Vatn MH, Ekbom A, et al. Incidence of Crohn’s disease in four counties of south-eastern Norway 1990-1993. A large prospective population-based study. Scand J Gastroenterol. 1996;31:350-4.
13. Bernstein CN, Wajda A, Svenson LW, et al. The epidemiology of inflammatory bowel disease in Canada: a population based study. Am J Gastroenterol. 2006;101:1559-68.
14. Jess T, Lofthus EV, Velayos FS, et al. Incidence and prognosis of colorectal dysplasia in inflammatory bowel disease: a population-based study from Olmsted County, Minnesota. Inflamm Bowel Dis. 2006;12:669-76.
15. Hildebrand H, Finkel Y, Grahnquist L, et al. Changing pattern of paediatric inflammatory bowel disease in northern Stockholm 1990-2001. Gut. 2003;52:1432-4.
16. Perminow G, Frigessi A, Rydning A, et al. Incidence and clinical presentation of IBD in children: comparison between prospective and retrospective data in a selected Norwegian population. Scand J Gastroenterol. 2006;41:1433-9.
17. Perminow G, Brackmann S, Lyckander LG, et al. Characterization in Childhood inflammatory bowel disease. A new population-based inception cohort from South-Eastern Norway, 2005-07, showing increased incidence in Crohn’s disease. Scand J Gastroenterol. 2008;43:1-11.
18. Lehtinen P, Ashorn M, Iltanen S, et al. Incidence trends of pediatric inflammatory bowel disease in Finland, 1987-2003, a nationwide study. Inflamm Bowel Dis. 2010; [Epub ahead of print]PMID: 218-459.
19. Manninen P, Karvonen A-L, Huhtala H, et al. The epidemiology of inflammatory bowel diseases in Finland. Scand J Gastroenterol. 2010;45:1063-7.
20. Lakatos L, Lakatos PL. Changes in the epidemiology of inflammatory bowel diseases. Orv Hetil. 2007;148:223-8.
21. Gearry RB, Richardson AK, Frampton CM, Dodgshun AJ, Barclay ML. Population-based cases control study of inflammatory bowel disease risk factors. J Gastroenterol Hepatol. 2010;25:325-33.
22. Wolthers F, Russel MG, Sijbrandij J, et al. Phenotype at diagnosis predicts recurrence rates in Crohn’s disease. Gut. 2006;55:1124-30.
23. Hoie O, Wolters F, Riis L, et al. Ulcerative colitis: Patients characteristics may predict 10-years disease recurrence in a European-wide population based cohort. Am J Gastroenterol. 2007;102:1692-701.
24. Goh KL. Shu-Dong XIAO Inflammatory bowel disease: A survey of the epidemiology in Asia. J Dig Dis. 2010;10:1-6.
25. Victoria CR, Sassak LY, Nunes HR. Incidence and prevalence rates of IBDs in midwestern of Sao Paulo State, Brazil. Arq Gastroenterol. 2009;46:20-5.
26. Kurata JH. Kantor-Fish, Frankl H. Crohn’s disease among etnic groups in a large health maintenance organization. Gastroenterology. 1992;102:1940-8.
27. Heresbach D, Gulwani-Alkolkar B, Lesser M, et al. Anticipation in Crohn’s disease may be influenced by gender and ethnicity of the transmitting parent. Am J Gastroenterol. 1998;93:2368-72.
28. Niv Y, Abuksis G, Fraser GM. Epidemiology of ulcerative colitis in Israel: A Survey of Israeli kibbutz settlements. Am J Gastroenterol. 2000;95:693-8.
29. Zheng JJ, Zhu XS, Huangfu Z, Gao ZX, Guo ZR, Wang Z. Crohn’s disease in mainland China: A systematic analysis of 50 years of research. Chin J Dig Dis. 2005;6:175-81.
30. Desai HG, Gupte PA. Increasing incidence of Crohn’s disease in India: is it related to improved sanitation? Indian J Gastroenterol. 2005;24:23-4.
31. Bernstein CN, Shanahan F. Disorders of a modern lifestyle: reconciling the epidemiology of inflammatory bowel diseases. Gut. 2008;57:1185-91.
32. Calkins BM, Lilienfeld AM, Garland CF, et al. Trends and incidence rates of ulcerative colitis and Crohn’s disease. Dig Dis Sci. 1984;29:913-20.
33. Garland CF, Lilienfield AM, Mendeloff AI, et al. Incidence rates of ulcerative colitis and Crohn’s disease in fifteen areas of the United States. Gastroenterology. 1981;81:1115-24.
34. Nerich V, Monnet E, Etienne OA, et al. Geographical variations of inflammatory bowel disease in France: a study based on national health insurance data. Inflamm Bowel Dis. 2006;12:218-26.
35. Kiledebo S, Breckan R, Norgaard K, et al. The incidence of Crohn’s disease in northern Norway from 1983 to 1986. Scand J Gastroenterol. 1989;24:1265-70.
36. Haug K, Schrumpf E, Halvorsen JF, et al. Epidemiology of Crohn’s disease in Western Norway. Scand J Gastroenterol. 1989;24:1271-5.
37. Smith LA, Rameshanker R, Healy J, et al. An unusual prevalence of inflammatory bowel disease in a multiethnic population-single centre UK data. Gut. 2010;59(3): 181.
38. Ott C, Obermaier F, Thieler S, et al. The incidence of inflammatory bowel disease in a rural region of southern Germany: a prospective population based study. Eur J Gastroenterol Hepatol. 2008;20:917-23.
39. Frank DNA, St Amand AL, Feldman RA, et al. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Nat Acad Sci. 2007;104:13780-8.
40. Hugot J-P, Alberti C, Berrebi D, Bingen E, Cezard J-P. Crohn’s disease: The cold chain hypothesis. Lancet. 2003;362:2012-5.
41. Forbes A, Kalantzis T. Crohn’s disease: the cold chain hypothesis. Int J Colorectal Dis. 2006;21:399-401.
42. Malekzadeh F, Alberti C, Nouraei M, et al. Crohn’s disease and early exposure to domestic refrigeration. Plos One. 2009;4(1):e4288.
43. Luther J, Dave M, Higgins PDR, Kao JY. Association between Helicobacter pylori infection and inflammatory bowel disease: A meta-analysis and systematic review of the literature. Inflamm Bowel Dis. 2009;16:1077-84.
44. Koloski N-A, Bret L, Radford-Smith G. Hygiene hypothesis in inflammatory bowel disease: A critical review of the literature. World J Gastroenterol. 2008;14:165-73.
45. Korzenik JR. Past and current theories of etiology of IBD: toothpaste, worms, and refrigerators. J Clin Gastroenterol. 2005;39(4):59-65.
46. Chacon O, Bermudez LE, Barletta RG. Johne’s disease, inflammatory bowel disease, and Mycobacterium paratuberculosis. Annu Rev Microbiol. 2004;58:329-63.
47. Bernstein CN, Blanchard JF, Rawsthorne P, Collins MT. Population-based case control study of seroprevalence of Mycobacterium paratuberculosis in patients with Crohn’s disease and ulcerative colitis. J Clin Microbiol. 2004;42:1129-35.
48. Feller M, Huwiler K, Stephan R, et al. Mycobacterium avium subspecies paratuberculosis and Crohn’s disease: a systematic review and meta-analysis. Lancet Infect Dis. 2007;7:607-13.
49. Ricanek P, Lothe SM, Szpinda I, et al. Paucity of mycobacteria in mucosal bowel biopsies from adults and children with early inflammatory bowel disease. J Crohn’s Colitis. 2010;4:561-6.
50. Darfeuille-Michaud A, Boudeau J, Bulois P, et al. High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn’s disease. Gastroenterology. 2004;127:412-21.
51. Sonnenberg A. Similar geographic variations of mortality and hospitalization associated with IBD and Clostridium difficile colitis. Inflamm Bowel Dis. 2010;16:487-93.
52. Hildebrand H. On the generality of the latitudinal diversity gradient. Am Nat. 2004;163:192-211.
53. Aamodt G, Bukholm G, Jahnsen J, et al. The association between water supply and inflammatory bowel disease based on a 1990-1993 cohort study in southeastern Norway. Am J Epidemiol. 2008;168:1065-72.
54. Lerner A. Aluminum is a potential environmental factor for Crohn’s disease induction. Extended hypothesis. Ann NY Acad Sci. 2007;1107:329-45.
55. Rezaie A, Parker RD, Abdollahi M. Oxidative stress and pathogenesis of inflammatory bowel disease: An epi- phenomenon or the cause? Dig Dis Sci. 2007;52:2015-21.
56. Hayes CE, Nashold FE, Froicu M, et al. The immunological functions of the vitamin D endocrine system. Cell Mol Biol (Noisy-le-Grand). 2003;49:277-300.
57. Ekbom A, Adami HO, Helmick CG, Jonzon A, Zack MM. Perinatal risk factors for inflammatory bowel disease: a case-control study. Am J Epidemiol. 1990;132:1111-9.
58. Klement E, Lysy J, Hoshen M, Avitan M, Goldin E, Israeli E. Childhood hygiene is associated with the risk for inflammatory bowel disease: A population-based study. Am J Gastroenterol. 2008;103:1775-82.
59. Radon K. Contact with farm animals in early life and juvenile inflammatory bowel disease: a case-control study. Pediatrics. 2007;120:354-61.
60. Wurzelmann JI, Lyles CM, Sandler RS. Childhood infections and the risk of inflammatory bowel disease. Dig Dis Sci. 1994;39:555-60.
61. Green C, Elliott L, Beaudoin C, Bernstein CN. A population-based ecologic study of inflammatory bowel disease: Searching for etiologic clues. Am J Epidemiol. 2006;164:615-23. discussion 624-28.
62. Montgomery SM, Lambe M, Wakefield AJ, Pounder RE, Ekbom A. Siblings and the risk of inflammatory bowel disease. Scand J Gastroenterol. 2002;37:1301-8.
63. Bengtson M-B, Solberg C, Aamodt G, et al. Clustering in time of familial IBD separates ulcerative colitis and Crohn’s disease. Inflam Bowel Dis. 2009;15:1867-74.
64. Lashner BA, Loftus EV. True or false? The hygiene hypothesis for Crohn’s disease. Am J Gastroenterol. 2006;101:1003-4.
65. Amre DK, Lambrette P, Law L, et al. Investigating the hygiene hypothesis as a risk factor in pediatric onset Crohn’s disease: a case-control study. Am J Gastroenterol. 2006;101:1005-11.
66. Bernstein CN, Rawsthorne P, Cheang M, Blanchard JF. A population-based case control study of potential risk factors for IBD. Am J Gastroenterol. 2006;101:993-1002.
67. Feeney MA, Murphy F, Clegg AJ, Trebble TM, Sharer NM, Snook JA. A case-control study of childhood environmental risk factors for the development of inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2002;14:529-34.
68. Sonnenberg A. Disability from inflammatory bowel disease among employees in West Germany. Gut. 1989; 30:367-70.
69. Sonnenberg A. Occupational distribution of inflammatory bowel disease among German employees. Gut. 1990;31:1037-40.
70. Solberg IC, Vatn MH, Hoie O, et al. Clinical course in Crohn’s disease: Results of a population based ten-year follow-up study. Clin Gastroenterol Hepatol. 2007;5:1430-8.
71. Mahid SS, Minor KS, Soto RE, et al. Smoking and inflammatory bowel disease: A metanalysis. Mayo Clin Proc. 2006;81:1462-71.
72. Russel RK, Farhodi R, Wilson M, et al. Perinatal passive smoke exposure may be more important than childhood exposure in the risk of developing childhood IBD. Gut. 2005;54:1500-1.
73. Regueiro M, Kevin EK, Onki C, et al. Cigarette smoking and age at diagnosis of inflammatory bowel disease. Inflamm Bowel Dis. 2005;11:42-7.
74. Bridger S, Lee JCW, Bjarnason L, et al. Inflammatory bowel disease. In siblings with similar genetic susceptibility for inflammatory bowel disease, smokers tend to develop Crohn’s disease and non-smokers develop ulcerative colitis. Gut. 2002;51:21-5.
75. Yamamoto T, Nakahigashi M, Saniabadi AR. Review article: diet and inflammatory bowel disease-epidemiology and treatment. Aliment Pharmacol Ther. 2009;30:99-112.
76. Graham TO, Kandil HM. Nutritional factors in inflammatory bowel disease. Gastroenterol Clin N Am. 2002;31:203-18.
77. Han PD, Burke A, Baldassano N, Rombeau JL, Lichtensein GR. Nutrition and inflammatory bowel disease. Gastroenerol Clin N Am. 1999;28:423-43.
78. Corrao C, Traguone A, Caprilli R, et al. Risk of inflammatory bowel disease attributable to smoking, oral contraception and breast feeding in Italy: A nationwide case-control study. Int J Epidemiol. 1998;27:397-404.
79. Klement E, Cohen RV, Boxman J, Joseph A, Reif S. Breastfeeding and risk of inflammatory bowel disease: a systematic review with meta-analysis. Am J Clin Nutr. 2004;80:1342-52.
80. Baron S, Turck D, Leplat C, et al. Environmental risk factors in paediatric inflammatory bowel diseases: a population based case control study. Gut. 2005;54:357-63.
81. Mikhailov TA, Furner SE. Breastfeeding and genetic factors in the etiology of inflammatory bowel disease in children. World J Gastroenterol. 2009;15:270-9.
82. Jantshou P, Morois S, Clavel-Chapelon F, Boutron-Ruault MC, Carbonell F. Animal protein intake and risk of inflammatory bowel disease: the E3N prospective study. Am J Gastroenterol. 2010;105:2195-201.
83. Persson P-G, Ahlbom A, Hellers G. Diet and inflammatory bowel disease: A case-control study. Epidemiology. 1992;3:47-52.
84. Amre DK, D’Souza S, Morgan K, et al. Imbalances in dietary consumption of fatty acids, vegetables, and fruits are associated with risk for Crohn’s disease in children. Am J Gastroenterol. 2007;102:2016-25.
85. Geerling BJ, Dagnelie PC, Badart-Smook A, Russel MG, Stockbrugger RW, Brummer RJ. Diet as a risk factor for the development of ulcerative colitis. Am J Gastroenterol. 2000;95:1008-13.
86. Sakamoto N, Kono S, Wakai K, et al. Dietary risk factors for inflammatory bowel disease: a multicenter case- control study in Japan. Inflamm Bowel Dis. 2005;11:154-63.
87. Maconi G, Ardizzone S, Cucino C, Bezzio C, Russo AG, Bianchi-Porro G. Pre-illness changes in dietary habits and diet as a risk factor for inflammatory bowel disease: a case-control study. World J Gastroenterol. 2010; 16:4297-304.
88. Shoda R, Matsueda K, Yamato S, Uemada N. Epidemiologic analysis of Crohn’s disease in Japan: increased dietary intake of n-6 polyunsaturated fatty acids and animal protein relates to the increased incidence of Crohn’s disease in Japan. Am J Clin Nutr. 1996;63:741-5.
89. Hart AR et al. Linoleic acid, a dietary n-6 polyunsaturated fatty acid, and aetiology of ulcerative colitis: a nested case-control study within a European prospective cohort study. Gut. 2009;58:1606-11.
90. Hart AR, Luben R, Olsen A, et al. Diet in the aetiology of ulcerative colitis: a European prospective cohort study. Digestion. 2008;77:57-64.
91. Azakura H, Suzuki K, Kitahora T, Morizane T. Is there a link between food and intestinal microbes and the occurrence of Crohn’s disease and ulcerative colitis? J Gastroenterol Hepatol. 2008;23:1794-801.
92. Martini GA, Brandes JW. Increased consumption of refined carbohydrates in patients with Crohn’s disease. Klin Wschr. 1976;54:367-71.
93. Penny WJ, Mayberry JF, Aggett Pj, et al. Relationship between trace elements, sugar consumption, and taste in Crohn’s disease. Gut. 1983;24:288-92.
94. Katschinski B, Logan RFA, Edmond M, Langman MJS. Smoking and sugar intake are separate but interactive risk factors in Crohn’s disease. Gut. 1988;29:1202-6.
95. Silkoff K, Hallak A, Yegena L, et al. Consumption of refined carbohydrate by patients with Crohn’s disease in Tel-Aviv-Yafo. Postgrad Med J. 1980;56:842-6.
96. Matsui T, Iida M, Fujishima M, et al. Increased sugar consumption in Japanese patients with Crohn’s disease. Gastroenterol Jpn. 1990;25:271.
97. Tragnone A, Valpiani D, Miglio F, et al. Dietary habits as risk factors for inflammatory bowel disease. Eur J Gastroenterol Hepatol. 1995;7:47-51.
98. James AH. Breakfast and Crohn’s disease. Br Med J. 1977;1:943-5.
99. Young CA, Sonnenberg A, Burns EA. Lymphocyte proliferation response to Baker’s yeast in Crohn’s disease. Digestion. 1994;55:40-3.
100. Mckenzie H, Main J, Pennington CR, Parrat D. Antibody to selected strains of Saccharomyces cervisiae (baker’s and brewer’s yeast) and candida albicans in Crohn’s disease. Gut. 1990;31:536-8.
101. Halfvarson J, Standaert-Vitse A, Jarnerot G, et al. Anti-saccharromyces cervisiae antibodies in twins with inflammatory bowel disease. Gut. 2005;54:1237-43.
102. Lee G, Buchman AL. DNA-driven nutritional therapy of inflammatory bowel disease. Nutrition. 2009;25:885-91.
103. Beaudet AL. Epigenetics and complex human disease: is there a role in IBD? J Pediatr Gastroenterol Nutr. 2008;46 Suppl 1:E2.
104. Lin Z, Hegarty JP, Cappel J, Yu W, Chen X, Faber P, Wang Y, Kelly A, Poritz L, Peterson B, Schreiber S, Fa JB, Koltun W. Identification of disease-associated DNA methylation in intestinal tissues from patients with inflammatory bowel disease. Clin Genet. 2010;Sep 16. doi: 10.1111/j.1399-0004.2010.01546.x. [Epub ahead of print]
105. Kosuda LL, Greiner DL, Bigazzi PE. Mercury-induced renal autoimmunity Changes in RT6+ T-lymphocytes of susceptible and resistant rats. Environ Health Perspect. 1993;101:178-85.
106. Perl DP, Fogarty U, Harpaz N, et al. Bacterial-metal interactions: the potential role of aluminum and other trace elements in the etiology of Crohn’s disease. Inflamm Bowel Dis. 2004;10:881-3.
107. Lomer MCE, Harvey RSJ, Evans SM, et al. Efficacy and tolerability of a low mictoparticle diet in a doubble blind, randomized, pilot study in Crohn’s disease. Eur J Gastroenterol Hepatol. 2001;13:101-6.
108. Cipola G, Crema F, Sacco S, Moro E, di Ponti F, Frigo G. Anti-inflammatory drugs and inflammatory bowel disease: Current perspectives. Pharmacol Res. 2002;46:1-6.
109. Bjarnason I, Takeutchi K. Intestinal permeability in the pathogenesis of NSAID-induced enteropathy. Scand J Gastroenterol. 2009;44 Suppl 19:23-9.
110. EI Miedany Y, Yossef S, Ahmed I, El Gafary M. The gastrointestinal safety and effect on disease activity of etoricoxib, a selective cox-2 inhibitor in inflammatory bowel diseases. Am J Gastroenterol. 2006;101:311-7.
111. Sandler RS, Wurzelmann JI, Lyles CM. Oral contraceptive use and the risk of inflammatory bowel disease. Epidemiology. 1992;3:374-8.
112. Zappata LB, Paulen MB, Cancino C, Marchbanks PA, Curtis KM. Contraceptive use among women with inflammatory bowel disease: A systematic review. Contraception. 2010;82:72-85.
113. Cornish JA, Tan E, Simillis C, Clark SK, Teare J, Tekkis PP The risk of oral contraceptives in the etiology of inflammatory bowel disease: a meta-analysis. Am J Gastroenterol. 2008;103:2394-400.
114. Okori Ni, Kane SV. Gender-related issues in the female inflammatory bowel disease patient. Expert Rev Gastroenterol Hepatol. 2009;3:145-54.
115. Tysk C, Jarnrot G. Seasonal variation in exacerbation of ulcerative colitis. Scand J Gastroenterol. 1993;28:95-6.
116. Moum B, Aadland E, Ekbom A, et al. Seasonal variation in the onset of ulcerative colitis. Gut. 1996;38:376-8.
117. Sonnenberg A. Date of birth in the occurrence of inflammatory bowel disease. Inflamm Bowel Dis. 2009;15:206-11.
118. Kahn RR, Lawson AD, Minnich LL, Martin K, Nasir A, Emmet MK, et al. Gastrointestinal norovirus infection associated with exacerbation of inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2009;48:328-33.
119. Aamodt G, Jahnsen J, Bengtson MB et al. Geographic distribution and ecological studies of inflammatory bowel disease in southeastern Norway in 1990-1993. Inflamm Bowel Dis. 2008;14 (7):984-91.
120. Lopez RD, Gabriel R, Cantero PJ, Moreno OR, Fernandez BM, Mate JJ. Association of MALTectomy (appendectomy and tonsillectomy) and inflammatory bowel disease: A familial case control study. Rev Esp Enferm Dig. 2001; 93:303-14.
121. Firouzi F, Bahari A, Aghazadeh R, Zali MR. Appendectomy, tonsillectomy, and risk of inflammatory bowel disease: A case control study in Iran. Int J Colorectal Dis. 2006;21:155-9.
122. Gearry RB, Richardson AK, Frampton CM, Dodshun AJ, Barclay ML. Population based cases control study of inflammatory bowel disease risk factors. J Gastroenterol Hepatol. 2010;25:227-8.
123. Lopez-Serrano P, Perez-Calle JL, Perez-Fernandez MT, Fernandez-Font JM, Boixeda deMiguel D, Fernandez- Rodriguez CM. Environmental risk factors in inflammatory bowel diseases. Investigating the hygiene hypothesis: a Spanish case control study. Scand J Gastroenterol. 2010;45:1464-71.
124. Kontroubakis IE, Vlachonicolis IG, Kapsoritakis A, et al. Appendectomy, tonsillectomy, and risk of inflammatory bowel disease: A case-controlled study in Crete. Dis Colon Rectum. 1999;42:225-30.