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A retrospective, case-control study on traditional environmental risk factors in inflammatory bowel disease in Vukovar-Srijem County, north-eastern Croatia, 2010



Traditional environmental risk factors in inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn’s disease (CD), were examined as part of the retrospective epidemiologic study conducted in Vukovar-Srijem County, north-eastern Croatia in 2010. The geographical variations in the frequency of IBD in Croatia have been observed, which is also the trend in the Central Eastern European region and Europe as a whole, indicating the influence of environmental and lifestyle factors. However, the data on the spread of environmental IBD risk factors are still limited. The purpose of this study was to analyse the traditional environmental risk factors in IBD on our cohort sample, including measles virus infection and vaccination (MMR vaccine—Mumps, Measles, Rubella), tonsillectomy, appendectomy, current and former cigarette smoking and use of oral contraceptives in women.


This retrospective, case-control study was performed as a part of a wider epidemiologic study aimed at assessing the incidence, prevalence and clinical expression of IBD, in Vukovar-Srijem County (population: 204,768; 2001), which is a lesser developed part of the continental Croatia that experienced deep demographic changes in the recent past. IBD patients were identified according to the hospital’s patient records. There were 119 UC patients and 31 CD patients of a total of 150 patients in the cohort. A total of 150 individuals, volunteers, not having a diagnosis of IBD, age- and sex-matched, were used as the control group. Information on examined risk factors were obtained from all subjects in a previously conducted interview. Patients were contacted personally or by phone and interviewed by a gastroenterologist.


There were no differences in the number of smokers, former smokers and non-smokers, between UC and CD patients and the controls, nor in the duration of smoking (years), in current smokers and ex-smokers. Only marginally significant longer time of non-smoking, in ex-smokers was found in IBD patients, compared to the controls, more pronounced in CD patients (p = 0.05). No difference was found in relation to tonsillectomy and risk of IBD. There was no difference in the number of female IBD patients and women from the controls using oral contraceptives. Duration (years) of oral contraceptives use was longer in women from the controls than in female IBD patients (p < 0.001). Frequency of appendectomy was the lowest in UC patients, compared to the controls and CD patients (3.4, 12.0 and 38.7 %, respectively) (p < 0.001). No difference was found in relation to measles virus infection and risk of IBD. MMR vaccination rates were higher in CD patients (90.3 %), compared to UC patients and the controls (74.8 and 67.3 %, respectively) (p = 0.026).


No association was found between smoking and tonsillectomy and risk of IBD. Our results do not support the idea of oral contraceptives use as a risk factor for IBD. Frequency of appendectomy was the lowest in UC patients, suggesting that appendectomy decreases the risk of UC, contributing the earlier results. MMR vaccination seemed to be associated with Crohn’s disease. These results can add value to our understanding of the increasing incidence of IBD in Croatia and other Central Eastern European countries and can be introductory to future large-scale research.

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  1. 1

    Mack CL, Gonzalez-Peralta RP, Gupta N, Leung D, Narkewicz MR, Roberts EA, North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition, et al. Differentiating ulcerative colitis from Crohn disease in children and young adults: report of a working group of the North American Society for pediatric gastroenterology, hepatology and nutrition and the Crohn’s and Colitis Foundation of America. J Pediatr Gastroenterol Nutr. 2007;44(5):653–74. doi:10.1097/MPG.0b013e318258328d.

    Article  Google Scholar 

  2. 2

    Cosnes J, Gower-Rousseau C, Seksik P, Cortot A. Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology. 2011;140(6):1785–94. doi:10.1053/j.gastro.2011.01.055.

    Article  PubMed  Google Scholar 

  3. 3

    Danese S, Fiocchi C. Ulcerative colitis. N Engl J Med. 2011;365(18):1713–25. doi:10.1056/NEJMra1102942.

    Article  CAS  PubMed  Google Scholar 

  4. 4

    Siegmund B, Zeitz M. Clinical aspects of inflammatory bowel disease. Eur J Immunol. 2009;39(8):2026–30. doi:10.1002/eji.200939601.

    Article  CAS  PubMed  Google Scholar 

  5. 5

    Shivananda S, Lennard-Jones J, Logan R, Fear N, Price A, Carpenter L, 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(5):690–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. 6

    Loftus EV. Clinical epidemiology of inflammatory bowel disease: incidence, prevalence and environmental influences. Gastroenterology. 2004;26(26):1504–17. doi:10.1053/j.gastro.2004.01.063.

    Article  Google Scholar 

  7. 7

    Molodecky NA, Soon IS, Rabi DM, Ghali WA, Ferris M, Chernoff G, et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology. 2012;142(1):46–54. doi:10.1053/j.gastro.2011.10.001.

    Article  PubMed  Google Scholar 

  8. 8

    Cho JH. Finding inflammatory bowel disease genes will lead to a cure. Can J Gastroenterol. 2006;20(10):641–2.

    PubMed Central  PubMed  Google Scholar 

  9. 9

    Abraham C, Cho JH. Inflammatory bowel disease. N Engl J Med. 2009;361:2066–78. doi:10.1056/NEJMra0804647.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. 10

    Baumgart DC (ed.). Crohn’s disease and ulcerative colitis: from epidemiology and immunobiology to a rational diagnostic and therapeutic approach. Springer; 2012. Chapter 2, Environmental factors in the epidemiology of inflammatory bowel disease; p. 17–38. doi:10.1007/978–1-4614-0998-4_2.

  11. 11

    Mikhailov TA, Furner SE. Breastfeeding and genetic factors in the etiology of inflammatory bowel disease in children. World J Gastroenterol. 2009;15(3):270–9. doi:

    Article  PubMed Central  PubMed  Google Scholar 

  12. 12

    Hansen TS, Jess T, Vind I, Elkjaer M, Nielsen MF, Gamborg M, et al. Environmental factors in inflammatory bowel disease: a case-control study based on a Danish inception cohort. J Crohns Colitis. 2011;5(6):577–84. doi:10.1016/j.crohns.2011.05.010.

    Article  PubMed  Google Scholar 

  13. 13

    Pezerović D, Klarin I, Žulj M, Majnarić Lj, Khaznadar E, Včev A. Incidence and prevalence of inflammatory bowel disease in Vukovar-Srijem County, Croatia, 1991–2000 and 2001–2010: a population-based study. Coll Antropol. 2014;38(1):115–23.

    PubMed  Google Scholar 

  14. 14

    Ebling B, Majnarić-Trtica Lj, Gmajnić R, Ebling Z, Vranješ Ž. Psycho-social aspects of measures aimed at decreasing prevalence of chronic diseases in the population of returnees in the Osijek Region, Croatia. Coll Antropol. 2007;31(2):441–50.

    PubMed  Google Scholar 

  15. 15

    Pezerović D, Žulj M, Klarin I, Majnarić Lj, Včev I, Včev A. Clinical expression of inflammatory bowel disease—a retrospective population-based cohort study; Vukovar-Srijem County, Croatia, 2010. Coll Antropol. 2013;37(3):919–27.

    PubMed  Google Scholar 

  16. 16

    Silverstein MD, Lashner BA, Hanauer SB, Evans AA, Kirsner JB. Cigarette smoking in Crohn’s disease. Am J Gastroenterol. 1989;84(1):31–3.

    CAS  PubMed  Google Scholar 

  17. 17

    Boyko EJ, Perera DR, Koepsell TD, Keane EM, Inui TS. Effects of cigarette smoking on the clinical course of ulcerative colitis. Scand J Gastroenterol.1988;23(9):1147–52.

    Article  CAS  PubMed  Google Scholar 

  18. 18

    Cosnes J, Beaugerie L, Carbonnei F, Gendre JP. Smoking cessation and the course of Crohn’s disease: an intervention study. Gastroenterol. 2001;120(5):1093–9.

    Article  CAS  Google Scholar 

  19. 19

    Beaugerie L, Massot N, Carbonnel F, Cattan S, Gendre JP, Cosnes J. Impact of cessation of smoking on the course of ulcerative colitis. Am J Gastroenterol. 2001;96(7):2113–6.

    Article  CAS  PubMed  Google Scholar 

  20. 20

    Higuchi LM, Khalili H, ChaN AT, Richter JM, Bousvaros A, Fuchs CS. A prospective study of cigarette smoking and the risk of inflammatory bowel disease in women. Am J Gastroenterol. 2012;107(9):1399–406. doi:10.1038/ajg.2012.196.Epub 2012 Jul 10.

    Article  PubMed Central  PubMed  Google Scholar 

  21. 21

    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(9):2394–400. doi:10.1111/j.1572-0241.2008.02064.x.

    Article  PubMed  Google Scholar 

  22. 22

    Khalili H, Higuchi LM, Ananthakrishnan NN, Manson JE, Feskanich D, Richter JM, et al. Hormone therapy increases risk of ulcerative colitis but not Crohn’s disease. Gastroenterology. 2012;143(5):1199–206. doi:10.1053/j.gastro.2012.07.096. (Epub 2012 July 27).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. 23

    Gilat T, Hacohen D, Lilos P, Langman MJ. Childhood factors in ulcerative colitis and Crohn’s disease. An international cooperative study. Scand J Gastroenterol. 1987;22(8):1009–24.

    Article  CAS  PubMed  Google Scholar 

  24. 24

    Parrello T, Pavia M, Angelillo IF, Monteleone G, Riegler G, Papi G, et al. Appendectomy is an independent protective factor for ulcerative colitis: results of a multicenter case control study. Ital J Gastroenterol Hepatol. 1997;29:208–13.

    CAS  PubMed  Google Scholar 

  25. 25

    Frisch M, Johansen C, Mellemkjaer L, Engels EA, Gridley G, Biggar RJ, et al. Appendectomy and subsequent risk of inflammatory bowel diseases. Surgery. 2001;130:36–43.

    Article  CAS  PubMed  Google Scholar 

  26. 26

    Radford-Smith GL, Edwards JE, Purdie DM, Pandeya N, Watson M, Martin NG, et al. Protective role of appendectomy on onset and severity of ulcerative colitis and Crohn’s disease. Gut. 2002;51:808–13. doi:10.1136/gut.51.6.808.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. 27

    Russel MG, Dorant E, Brummer RJ, van de Kruijs MA, Muris JW, Bergers JM, Goedhard J, et al. Appendectomy and the risk of developing ulcerative colitis or Crohn’s disease: results of a large case-control study. South Limburg Inflammatory Bowel Disease Study Group. Gastroenterology. 1997;113(2):377–82.

    Article  CAS  PubMed  Google Scholar 

  28. 28

    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(2):325–33. doi:10.1111/j.1440-1746.2009.06140.x.

    Article  PubMed  Google Scholar 

  29. 29

    Koutroubakis IE, Vlachonikolis IG, Kapsoritakis A, Spanoudakis S, Roussomoustakaki M, Mouzas IA, et al. Appendectomy, tonsillectomy and risk of inflammatory bowel disease: case-controlled study in Crete. Dis Colon Rectum. 1999;42(2):225–30.

    Article  CAS  PubMed  Google Scholar 

  30. 30

    Thompson NP, Montgomery SM, Pounder RE, Wakefield AJ. Is measles vaccination a risk factor for inflammatory bowel disease? Lancet. 1995;345(8957):1071–4.

    Article  CAS  PubMed  Google Scholar 

  31. 31

    Davis R, Kramarz P, Bohlke K, Benson P, Thompson RS, Mullooly J, et al. Measles-Mumps-Rubella and other measles-containing vaccines do not increase the risk for inflammatory bowel disease. A case-control study from the Vaccine Safety Datalink Project. JAMA Pediatrics. 2001;155(3):354–9. doi:10.1001/archpedi.155.3.354.

    CAS  Google Scholar 

  32. 32

    Demicheli V, Rivetti A, Debalini MG, Di Pietrantonj C. Vaccines for measles, mumps and rubella in children. Cochrane Database Syst Rev. 2012;2:CD004407.doi:10.1002/14651858.CD004407.pub3.

    PubMed  Google Scholar 

  33. 33

    Ekbom A, Wakefield AJ, Zack M, Adami HO. Perinatal measles infection and subsequent Crohn’s disease. Lancet. 1994;344(8921):508–10.

    Article  CAS  PubMed  Google Scholar 

  34. 34

    Davis RL, Bohlke K. Measles vaccination and inflammatory bowel disease: controversy laid to rest?. Drug Saf. 2001;24(13):939–46.

    Article  CAS  PubMed  Google Scholar 

  35. 35

    Lakatos L, Lakatos PL. Is the incidence and prevalence of inflammatory bowel diseases increasing in Eastern Europe?. Postgrad Med J. 2006;82(967):332–7. doi:10.1136/pgmj.2005.042416.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. 36

    Lakatos L, Mester G, Erdelyi Z, Balogh M, Szipocs I, Kamaras G, et al. Striking elevation in incidence and prevalence of inflammatory bowel disease in a province of western Hungary between 1977–2001. World J Gastroenterol. 2004;10(3):404–9.

    PubMed  Google Scholar 

  37. 37

    Mijandrusic Sincic B, Vucelic B, Persic M, Brncic N, Jurisic Erzen D, Radakovic B, et al. Incidence of inflammatory bowel disease in Primorsko-goranska county, Croatia, 2000–2004: a prospective population-based study. Scand J Gastroenterol. 2006;4(4):437–44.

    Article  Google Scholar 

  38. 38

    Klarin I, Majnaric Lj, JovanovicZ, Nakic D, Vcev I, Vcev A. Epidemiology and clinical presentation of inflammatory bowel disease in Zadar County, Croatia. Coll Antropol. 2013;37(4):1161–70.

  39. 39

    Lovasz BD, Lakatos l, Horvath A, Pandur T, Erdelyi Z, Balogh M, et al. Incidence rates and disease course of paediatric inflammatory bowel diseases in western Hungary between 1977 and 2011. Dig Liver Dis.2014;46(5):405–11.

    Article  PubMed  Google Scholar 

  40. 40

    Urlep d Trop TK Blagus R Orel R. Incidence and phenotypic characteristics of paediatric IBD in northeastern Slovenia, 2002–2010. J Pediatr Gastroenterol Nutr. 2014;58(3):325–32.

    Article  PubMed  Google Scholar 

  41. 41

    Gent AE, Hellier MD, Grace RH, Swarbrick ET, Coggon D. Inflammatory bowel disease and domestic hygiene in infancy. Lancet. 1994;343(8900):766–7.

    Article  CAS  PubMed  Google Scholar 

  42. 42

    Hlavaty T, Toth J, Koller T, Krajcovicova A, Oravcova S, Zelinkova Z, et al. Smoking, breastfeeding, physical inactivity, contact with animals and size of the family influence the risk of inflammatory bowel disease: a Slovak case-control study. United European Gastroenterol J. 2013;1(2):109–19.

    Article  PubMed Central  PubMed  Google Scholar 

  43. 43

    Lakatos PL, Fischer S, Lakatos L, Gal I, Papp J. Current concept on the pathogenesis of IBD—crosstalk between genetic and microbial factors: pathogenetic bacteria and altered bacterial sensing or changes in mucosal integrity take “toll”? World J Gastroenterol. 2006;12(12):1829–41.

    PubMed Central  CAS  PubMed  Google Scholar 

  44. 44

    Burisch J, Pederson N, Cukovic-Cavka S, Turk N, Kaimakliotis I, Duricova D, et al. Environmental factors in a population-based inception cohort of IBD patients in Europe—an ECCO-EpiCom study. J Crohns Colitis. 2014;8(7):607–16.

    Article  CAS  PubMed  Google Scholar 

  45. 45

    Ng SC, Bernstein CN, Vatn MH, Lakatos PL, Loftus EV Jr, Tysk C, et al. Geographical variability and environmental risk factors in IBD. Gut. 2013;62(4):630–49.

    Article  PubMed  Google Scholar 

  46. 46

    Newman B, Siminovitch KA. Recent advances in the genetics of inflammatory bowel disease. Curr Opin Gastroenterol. 2005;21(4):401–7.

    PubMed  Google Scholar 

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Correspondence to Ljiljana Majnarić PhD.

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Vcev, A., Pezerovic, D., Jovanovic, Z. et al. A retrospective, case-control study on traditional environmental risk factors in inflammatory bowel disease in Vukovar-Srijem County, north-eastern Croatia, 2010. Wien Klin Wochenschr 127, 345–354 (2015).

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  • Inflammatory bowel disease
  • Environmental risk factors
  • Retrospective case-control study
  • North-eastern Croatia