Short summary

One out of two hundred Danes suffer from IBD. While some patients have a mild disease course without any complications, other patients develop complications such as arthritis, pyoderma and colorectal cancer (CRC).

Using genetic analysis, we can identify genes involved in the biological processes of the disease and thus gain an insight into the development of the disease and the different courses it might take. We have extensive knowledge within this topic which is documented by our performed studies concerning the mechanisms underlying the development of chronic intestinal inflammation and cancer in the intestinal tract.

We will collect nationwide pathological samples available from relevant patients. We will extract DNA from the specimens to assess genotype distribution of controls and cases using a case-case and case-control study design.

Thereby we expect to identify genetic markers for the developing of distinct IBD-subtypes and to gain a new insight into the pathological mechanisms of the diseases.

Rationale

The main forms of IBD are Crohn's disease (CD) and ulcerative colitis (UC). Both are considered to represent autoimmune diseases, meaning that the body's own immune system attacks components of the digestive system. The symptoms of CD and UC are abdominal pain, rectal bleeding and diarrhea. Associated diseases include arthritis, pyoderma gangrenosum and an increased risk of the development of CRC. While the symptoms are similar, the location of the diseases varies. CD can affect the entire gastrointestinal tract, while UC, in most cases, involves the rectum and varying portions of the colon. The exact cause of the diseases is not yet fully understood, but a number of genetic and environmental factors, like smoking, hormone therapy and appendectomy contribute. The highest incidence rates and prevalence are found in northern Europe, the UK and the U.S.A., with the incidence rates having stabilized over the past years. Meanwhile, rates have risen in low incidence areas, such as southern Europe and Asia, as well as most developing countries.

Description of the cohort

Using information from the National Patient Registry, the Danish Cancer Registry, the CPR Registry and the Registry of Pathology, we will identify cases with available pathological material throughout Denmark. Patients diagnosed with one or more of the following diagnoses are included in the initial cohort: Crohn's disease (DK50), ulcerative colitis (DK51), microscopic colitis (DK52), malabsorption (DK90), colon irritabile (DK58), cholangitis (DK83), liver diseases (DK70-DK77), biliary diseases (DK80-DK84), cancer in oral cavity, pharynx or digestive organs (DC00-DC26).

Furthermore, DNA from blood samples of 1,050 IBD cases and 796 healthy controls (blood donors) have already been sampled and genotyped. These samples will also be included in the study.

Data and biological material

DNA from all participants will be sampled and genotyped.

We expect to retrieve the following data: diagnosis, treatment response, age, gender, disease location/distribution/severity/course, age at diagnosis, smoking status, operations, concomitant medication, associated diseases, and familiar disposition.

Subprojects

OP_124: Validation of diagnosis codes in patients with inflammatory bowel disease (IBD)
Pre-graduate Student, Camilla Rye, OPEN Odense Patient data Explorative Network, Odense University Hospital

OP_172: Use of pathological samples to clarify the interplay of gastrointestinal inflammation and colorectal cancer
PhD-student, Katrine Svenningsen, Research Department of Molecular Diagnostics and Clinical Research, Institute of Regional Health Research, Sygehus

Collaborating researchers and departments

Research Department of Molecular Diagnostics and Clinical Research, Institute of Regional Health Research, Sygehus Sønderjylland

• PhD-student Katrine Svenningsen, MSc
• Associate Professor and Main Supervisor Vibeke Andersen, MD

Center for Clinical Research, Department of Clinical Medicine, Aalborg University, Sygehus Vendsyssel

• Clinical Professor and Supervisor Ulrik Baandrup, MD

Department of Clinical Pathology, Sygehus Lillebælt, Vejle

• Supervisor Rikke Hjarnø Hagemann-Madsen, MD

OPEN Odense Patient data Explorative Network, Odense University Hospital

• Professor and Supervisor Anders Green, MD, PhD

National Institute of Occupational Health

• Professor and Supervisor Ulla Vogel

Department of Clinical Molecular Biology, Akershus University Hospital, University of Oslo, Norway

• Professor and Collaboration Partner Stephan Brackmann

Institute of Clinical Molecular Biology, Christian-Albrechts University, Kiel

• Professor and Collaboration Partner Andre Franke

Publications associated with the project

Polymorphisms in the Inflammatory Pathway Genes TLR2, TLR4, TLR9, LY96, NFKBIA, NFKB1, TNFA, TNFRSF1A, IL6R, IL10, IL23R, PTPN22, and PPARG Are Associated with Susceptibility of Inflammatory Bowel Disease in a Danish Cohort. / Bank S, Skytt Andersen P, Burisch J, Pedersen N, Roug S, Galsgaard J et al. PloS one. 2014 jun 27;9(6). e98815.