Case Control Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 7, 2020; 26(25): 3611-3624
Published online Jul 7, 2020. doi: 10.3748/wjg.v26.i25.3611
Risk factors associated with inflammatory bowel disease: A multicenter case-control study in Brazil
Valéria Cristina Loureiro Salgado, Ronir Raggio Luiz, Neio Lucio Fernandes Boéchat, Isabella Sued Leão, Bianca do Carmo Schorr, José Miguel Luz Parente, Daniela Calado Lima, Eduardo Santos Silveira Júnior, Genoile Oliveira Santana Silva, Neogélia Pereira Almeida, Andrea Vieira, Maria Luiza Queiroz de Bueno, Júlio Maria Chebli, Érika Ruback Bertges, Luísa Martins da Costa Brugnara, Columbano Junqueira Neto, Stefania Burjack Gabriel Campbell, Luana Letiza Discacciati, João Paulo Silva Cézar, Tiago Nunes, Gilaad G Kaplan, Cyrla Zaltman
Valéria Cristina Loureiro Salgado, Isabella Sued Leão, Bianca do Carmo Schorr, Cyrla Zaltman, Division of Gastroenterology, Department of Internal Medicine, Clementino Fraga Filho Hospital, Federal University of Rio de Janeiro, Rio de Janeiro 21940-230, Brazil
Ronir Raggio Luiz, Institute for Studies in Public Health, Federal University of Rio de Janeiro, Rio de Janeiro 21940-230, Brazil
Neio Lucio Fernandes Boéchat, Multidisciplinary Research Laboratory, Clementino Fraga Filho Hospital, Institute of Thoracic Diseases, Faculty of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21940-230, Brazil
José Miguel Luz Parente, Daniela Calado Lima, Eduardo Santos Silveira Júnior, Division of Gastroenterology, Department of Internal Medicine, Hospital University, Faculty of Medicine, Federal University of Piauí, Piauí 64049-550, Brazil
Genoile Oliveira Santana Silva, Neogélia Pereira Almeida, Division of Gastroenterology, Inflammatory Bowel Disease Outpatient Clinic, Roberto Santos General Hospital (HGRS) of the Bahia State Department of Health, Bahia 40110-060, Brazil
Andrea Vieira, Maria Luiza Queiroz de Bueno, Division of Gastroenterology, Inflammatory Bowel Disease Outpatient Clinic, Irmandade Santa Casa da Misericórdia of São Paulo, São Paulo 01221020, Brazil
Júlio Maria Chebli, Érika Ruback Bertges, Luísa Martins da Costa Brugnara, Division of Gastroenterology, Department of Internal Medicine, Hospital University, Faculty of Medicine, Federal University of Juiz de Fora, Minas Gerais 36036-247, Brazil
Columbano Junqueira Neto, Stefania Burjack Gabriel Campbell, Luana Letiza Discacciati, João Paulo Silva Cézar, Division of Gastroenterology, Inflammatory Bowel Disease Outpatient Clinic, Federal District Base Hospital, Brasília 70330-150, Brazil
Tiago Nunes, Gastrointestinal Physiology, Institute of Nutritional Science, Nestle Research Center, Lausanne 1000, Switzerland
Gilaad G Kaplan, Departments of Medicine and Community Health Sciences, University of Calgary, Calgary T2N4Z6, Canada
Author contributions: Salgado VCL, Boéchat NLF and Zaltman C designed the study; Salgado VCL, Zaltman C, Parente JML, Silva GOS, Vieira A, Chebli JM, Junqueira Neto C coordinated and provided the collection of all data; Salgado VCL, Leão IS, Schorr BC, Lima DC, Silveira Júnior ES, Ameilda NP, de Bueno MLQ, Bertges ÉR, Brugnara LMC, Campbell SBG, Discacciati LL and Cézar JPS made the structured interviews and collected patient's data from clinical reports; Salgado VCL and Luiz RR organized and analyzed the data; Salgado VCL, Zaltman C, Nunes T and Kaplan GG were involved in writing and editing the manuscript. All authors read and approved the final manuscript.
Supported by Carlos Chagas Filho Rio de Janeiro State Research Foundation (Faperj), No. 100.044/2011.
Institutional review board statement: The study was approved by the ethics committee of Clementino Fraga Filho University Hospital/ UFRJ (Rio de Janeiro, Brazil).
Informed consent statement: All patients gave informed consent.
Conflict-of-interest statement: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Cyrla Zaltman, MD, PhD, Associate Professor, Postdoc, Division of Gastroenterology, Department of Internal Medicine, Clementino Fraga Filho Hospital, Federal University of Rio de Janeiro, Rodolpho Paulo Rocco Street 255, Ilha do Fundão, Rio de Janeiro 21940-230, Brazil. c.zaltman@gmail.com
Received: December 25, 2019
Peer-review started: December 25, 2019
First decision: January 19, 2020
Revised: June 16, 2020
Accepted: June 18, 2020
Article in press: June 18, 2020
Published online: July 7, 2020
Abstract
BACKGROUND

The etiology of inflammatory bowel disease (IBD) is unknown, but it is believed to be multifactorial. The hygiene hypothesis proposes that better hygiene conditions would lead to less infectious disease during childhood and favor the development of immune-mediated diseases.

AIM

To test the hygiene hypothesis in IBD by assessing the environmental risk factors associated with IBD development in different regions of Brazil with diverse socioeconomic development indices.

METHODS

A multicenter case-control study was carried out with 548 Crohn’s disease (CD) and 492 ulcerative colitis (UC) outpatients and 416 healthy controls, from six IBD centers within different Brazilian states at diverse socioeconomic development stages. A semi-structured questionnaire with 87 socioeconomic and environmental questions was applied. Logistic regression model was created to assess the odds ratio (OR) with P value and 95% confidence intervals (CI).

RESULTS

Predictive variables for both diseases (CD and UC) were women [odd ratios (OR) = 1.31; OR = 1.69], low monthly family income (OR = 1.78; OR = 1.57), lower number of cohabitants (OR = 1.70; OR = 1.60), absence of vaccination (OR = 3.11; OR = 2.51), previous history of bowel infections (OR = 1.78; OR = 1.49), and family history of IBD (OR = 5.26; OR = 3.33). Associated risk factors for CD were age (18-39 years) (OR = 1.73), higher educational level (OR = 2.22), absence of infectious childhood diseases (OR = 1.99). The UC predictive variables were living in an urban area (OR = 1.62), inadequate living conditions (OR = 1.48) and former smokers (OR = 3.36). Appendectomy was a risk factor for CD (OR = 1.58) with inverse association with UC (OR = 4.79). Consumption of treated and untreated water was associated with risk of CD (OR = 1.38) and UC (OR = 1.53), respectively.

CONCLUSION

This is the first examining environmental exposures as risk factors for inflammatory bowel disease in Brazil. Most of the variables associated with disease risk support the role of the hygiene hypothesis in IBD development.

Keywords: Crohn’s disease, Ulcerative colitis, Risk factors, Environmental factors, Hygiene hypothesis

Core tip: Brazil is a country with continental dimensions comprising an ethnically diverse population living in different regions with extreme socioeconomic differences. The country is the perfect setting to test the hygiene hypothesis in inflammatory bowel disease development. Thus, the aim of this study was to identify inflammatory bowel disease environmental risk factors across different geographical regions in Brazil and evaluate if the hygiene hypothesis might explain interregional differences in prevalence and incidence.