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I-SCAN: Risk of colorectal cancer in inflammatory bowel disease

Risk of colorectal cancer in inflammatory bowel disease

– a multinational cohort study.

Photo: Colourbox

About the project

I-SCAN (IBD – Scandinavian CANcer in IBD study) is a collaborative effort between the Clinical Effectiveness Research Group at the University of Oslo, Karolinska Institutet in Stockhom, Sweden, and Center for Clinical Research and Prevention at Bispebjerg and Frederiksberg Hospital in Denmark. Principal investigator (PI) is Mette Kalager and national PI’s are Weimin Ye in Sweden and Tine Jess in Denmark. I-SCAN also collaborates with Miguel Hernan at the Harvard T.H. Chan School of Public Health in Boston, U.S.

General aim

The current project will provide new cancer risk estimates for patients with Inflammatory bowel diseases (ulcerative colitis and Crohn’s disease). This will enable us to implement effective and cost-effective treatment and surveillance strategies for these patients.

Specific aims

  1. To quantify overall cancer risk among patients with IBD, modified by age at diagnosis, extent of disease, follow-up time and pharmacological treatment.
  2. To quantify the effect, if any, of IBD therapies on the risk of cancer
  3. To develop and validate a prediction model for colorectal cancer risk in IBD patients.

Background

Inflammatory bowel diseases (ulcerative colitis and Crohn’s disease) – are the most common non-malignant chronic diseases affecting the large bowel.

Patients with inflammatory bowel disease, and notably those with ulcerative colitis, are at increased risk of developing colorectal cancer. In 1990, we published the first large-scale population-based prospective study of cancer risk among patients with ulcerative colitis and Crohn’s disease.1,2 At least two factors might have modified and indeed reduced their cancer risk. Firstly, improved pharmacological treatment such as immunomodulatory agents (thiopurines and tumor necrosis factor-alpha antagonists).3,4 Secondly, patients with inflammatory bowel disease are more extensively and systematically under colonoscopic surveillance with biopsies and even prophylactic colectomy. Such surveillance may reduce risk of colorectal cancer. However, although multiple studies have tried to update our findings from 1990, their estimates remain uncertain because of challenges in design, size, methodology or reliable data access.5,6 Therefore, it is currently unclear to which extent the results published in 1990 are generalizable to patients treated for inflammatory bowel disease today.

The current project includes unique, large-scale studies to disentangle the risk of cancer in patients with inflammatory bowel disease in our current, modern era of medicine. Prerequisites for this project may exist only in the Nordic countries due to their excellent infrastructure for epidemiologic research. We also take advantage of the great experience we have within the research consortium of this project, which has proven to produce cutting-edge scientific results of this magnitude and novelty in the past.7-9

Registry-based research

We intend to develop the largest ever population-based cohort of patients with incident IBD (ulcerative colitis or Crohn’s disease). This project is possible because of the characteristics of health data collection in Scandinavian countries, which are uncommon in the rest of the world (Figure 1). We will collect data on all patients with IBD in Norway, Sweden and Denmark from 1970 until today. We aim to link multiple data sources, including high quality, virtually complete, nation-wide registers of cancer incidence (Cancer Registry), in-patient care (Patient Registry) (with codes for surgical procedures and all discharge diagnoses), prescribed drugs (Prescription Registry), immigration (Population Statistics), and dates as well as causes of death (Death Registry) (figure 1). Combination of these data sources gives detailed follow-up data that enable us to achieve our ambitious aims.

Financing

The study is funded partly by grants from the South East Regional Health Authority in Norway.

Start - finish

2015 - 2021

References

1. Ekbom A, Helmick C, Zack M, Adami HO. Ulcerative colitis and colorectal cancer. A population-based study. N Engl J Med 1990;323:1228-33

2. Ekbom A, Helmick C, Zack M, Adami HO. Increased risk of large-bowel cancer in Crohn's disease with colonic involvement. Lancet 1990;336:357-9

3. Jess T, Lopez A, Andersson M, Beaugerie L, Peyrin-Biroulet L. Thiopurines and risk of colorectal neoplasia in patients with inflammatory bowel disease: a meta-analysis. Clin Gastroenterol Hepatol. 2014 Nov;12(11):1793-1800

4. Nyboe Andersen N, Pasternak B, Basit S, Andersson M, Svanström H, Caspersen S, Munkholm P, Hviid A, Jess T. Association between tumor necrosis factor-α antagonists and risk of cancer in patients with inflammatory bowel disease. JAMA. 2014 Jun 18;311(23):2406-13

5. Adami HO, Bretthauer M, Emilsson L, Hernán MA, Kalager M, Ludvigson JF et al. The continuing uncertainty about cancer risk in inflammatory bowel disease. Gut 2016;65:889-93

6. Jess T, Simonsen J, Jørgensen KT, Pedersen BV, Nielsen NM, Frisch M. Decreasing risk of colorectal cancer in patients with inflammatory bowel disease over 30 years. Gastroenterology. 2012 Aug;143(2):375-81.e1

7. Løberg M. Kalager M, Holme Ø, Hoff G, Adami H-O, Bretthauer M. Long-term colorectal cancer mortality after adenoma removal. N Engl J Med 2014;371:799-807

8. Holme Ø, Løberg M. Kalager M, Bretthauer M, et al. Effect of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality: A randomized clinical trial. JAMA 2014;312:1-10

9. Kalager M, Zelen M, Langmark F, Adami HO. Effect of screening mammography on breast-cancer mortality in Norway. N Engl J Med 2010;363:1203-10

Tags: Nordic, USA, polyps, cancer, IBD
Published Nov. 24, 2015 2:12 PM - Last modified Sep. 2, 2019 10:58 AM

Contact

Principal Investigator (PI)
Mette Kalager, Prof.

Oslo University Hospital
University of Oslo

Participants

Detailed list of participants