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Original research
Inflammatory bowel disease and risk of small bowel cancer: a binational population-based cohort study from Denmark and Sweden
  1. Jordan E Axelrad1,
  2. Ola Olén2,3,4,
  3. Michael C Sachs2,
  4. Rune Erichsen5,6,
  5. Lars Pedersen5,
  6. Jonas Halfvarson7,
  7. Johan Askling2,
  8. Anders Ekbom2,
  9. Henrik Toft Sørensen5,
  10. Jonas F Ludvigsson8,9,10,11
  1. 1Inflammatory Bowel Disease Center at NYU Langone Health, Division of Gastroenterology, Department of Medicine, New York University School of Medicine, New York, New York, USA
  2. 2Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden
  3. 3Sachs’ Children and Youth Hospital, Stockholm South General Hospital, Stockholm, Sweden
  4. 4Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
  5. 5Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
  6. 6Department of Surgery, Randers Regional Hospital, Randers, Denmark
  7. 7Department of Gastroenterology, Faculty of Medicine and Health, School of Health and Medical Sciences, Örebro University, Örebro, Sweden
  8. 8Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  9. 9Department of Pediatrics, Orebro University Hospital, Örebro, Sweden
  10. 10Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, United Kingdom
  11. 11Department of Medicine, Columbia University College of Physicians and Surgeons, New York, United States
  1. Correspondence to Dr Jordan E Axelrad, New York University School of Medicine, New York, NY 10016-6402, USA; Jordan.Axelrad{at}nyulangone.org

Abstract

Objective Crohn’s disease (CD) is associated with increased risk of small bowel cancer (SBC), but previous studies have been small. We aimed to examine the risk of incident SBC and death from SBC in patients with inflammatory bowel disease (IBD).

Design In a binational, population-based cohort study from Sweden and Denmark of patients with IBD during 1969–2017 and matched reference individuals from the general population, we evaluated the risk of incident SBC and death from SBC. Cox regression was used to estimate adjusted hazard ratios (aHRs).

Results We identified 161 896 individuals with IBD (CD: 47 370; UC: 97 515; unclassified IBD: 17 011). During follow-up, 237 cases of SBC were diagnosed in patients with IBD (CD: 24.4/100 000 person-years; UC: 5.88/100 000 person-years), compared with 640 cases in reference individuals (2.81/100 000 person-years and 3.32/100 000 person-years, respectively). This corresponded to one extra case of SBC in 385 patients with CD and one extra case in 500 patients with UC, followed up for 10 years. The aHR for incident SBC was 9.09 (95% CI 7.34 to 11.3) in CD and 1.85 (95% CI 1.43 to 2.39) in UC. Excluding the first year after an IBD diagnosis, the aHRs for incident SBC decreased to 4.96 in CD and 1.69 in UC. Among patients with CD, HRs were independently highest for recently diagnosed, childhood-onset, ileal and stricturing CD. The relative hazard of SBC-related death was increased in both patients with CD (aHR 6.59, 95% CI 4.74 to 9.15) and patients with UC (aHR 1.57; 95% CI 1.07 to 2.32).

Conclusion SBC and death from SBC were more common in patients with IBD, particularly among patients with CD, although absolute risks were low.

  • inflammatory bowel disease
  • Crohn's disease
  • ulcerative colitis
  • cancer
  • adenocarcinoma
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Footnotes

  • Twitter @DrJordanAxelrad, @@ludvigsson

  • JEA and OO contributed equally.

  • Contributors Guarantor: OO. Study concept and design: all coauthors. Acquisition of data: OO, JFL, LP, RE and HTS. Analysis: MCS and OO had access to all the data and performed all analyses. MCS, OO and JA designed the figures. Funding: OO, JFL, RE, MCS and JA. Writing first draft of the manuscript: JA, OO and JFL. Critical revision of the manuscript for important intellectual content and approval of final version: all coauthors.

  • Funding JA was supported by grants from the NYU School of Medicine. OO was supported by grants from the Swedish Medical Society (Project grants; Fund for Research in Gastroenterology and Ihre Foundation), Mag-tarmfonden, Karolinska Institutet Foundations, the Young Scholar Award from the Strategic Research Area Epidemiology Program at Karolinska Institutet and the Regional Agreement on Medical Training and Clinical Research between Stockholm County Council (ALF) and the Karolinska Institutet (ALF). RE was supported by research grants from the Danish Cancer Association and the Novo Nordisk Foundation. JA was supported by the Swedish Cancer Society, the Stockholm County Council (ALF), the Swedish Research Council, the Swedish Heart Lung Foundation and the Nordic Research Council. JFL was supported by the FORTE Foundation and the Swedish Cancer Foundation. The project was also supported by a grant from the Independent Research Fund Denmark. OO had full access to all the data and had final responsibility for the decision to submit the manuscript for publication. He is the guarantor of the manuscript.

  • Disclaimer None of the funding organisations had any role in the design and conduct of the study; in the collection, management and analysis of the data or in the preparation, review and approval of the manuscript.

  • Competing interests JA has served as a consultant for Aetion and BioFire diagnostics. OO has been PI on projects at Karolinska Institutet partly financed by investigator-initiated grants from Janssen and Ferring. He also reports a grant from Pfizer in the context of a national safety monitoring programme. None of those studies has any relation to the present study. The Karolinska Institutet has received fees for Olén’s lectures and participation on advisory boards from Janssen, Ferring, Takeda and Pfizer regarding topics not related to the present study. JA acts or has acted as PI for agreements between Karolinska Institutet and grants from AbbVie, Bristol-Myers Squibb, Eli Lilly, Merck, Pfizer, Roche, Samsung Bioepis, Sanofi and UCB, mainly in the context of a national safety monitoring programme for immunomoduators in rheumatology (ARTIS). JLF coordinates a study unrelated to the present study on behalf of the Swedish IBD Quality Register (SWIBREG). That study has received funding from Janssen. JH has served as speaker and/or advisory board member for AbbVie, Celgene, Celltrion, Ferring, Hospira, Janssen, MEDA, Medivir, MSD, Olink Proteomics, Pfizer, Prometheus Laboratories, Sandoz/Novartis, Shire, Takeda, Tillotts Pharma, Vifor Pharma and UCB. He also has received grant support from Janssen, MSD and Takeda. The Department of Clinical Epidemiology, Aarhus University Hospital, receives funding for other studies from companies in the form of research grants to (and administered by) Aarhus University. None of these studies has any relation to the present study.

  • Patient and public involvement Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Ethics approval This study was approved by the Ethics Review Board in Stockholm (2007/785-31/5; 2011/1509–32; 2015/0004–31, 2014/1287-31/4 and 2016/192-31/2) and by the Danish Data Protection Board.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information. No additional data available due to Swedish and Danish regulation.

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