Inflammatory Bowel Disease and Pancreatic Cancer

A Scandinavian Register-based Cohort Study 1969-2017

Åsa H. Everhov; Rune Erichsen; Michael C. Sachs; Lars Pedersen; Jonas Halfvarson; Johan Askling; Anders Ekbom; Jonas F. Ludvigsson; Henrik Toft Sørensen; Ola Olén

Disclosures

Aliment Pharmacol Ther. 2020;52(1):143-154. 

In This Article

Abstract and Introduction

Abstract

Background: Patients with inflammatory bowel disease (IBD) have an increased risk of cancer.

Aim: To assess the risk of pancreatic cancer in IBD compared to the general population.

Methods: Patients with incident IBD 1969–2017 were identified in Danish and Swedish National Patient Registers and through biopsy data, and were matched to IBD-free reference individuals by sex, age, place of residence and year of IBD diagnosis. We linked data to Cancer and Causes of Death Registers and examined the absolute and relative risks of pancreatic cancer and pancreatic cancer death.

Results: Among 161 926 patients followed for 2 000 951 person years, 442 (0.27%) were diagnosed with pancreatic cancer compared to 3386 (0.21%) of the 1 599 024 reference individuals. The 20-year cumulative incidence was 0.34% (95% confidence interval 0.30–0.38) vs 0.29% (0.28–0.30). The incidence rate was 22.1 (20.1–24.2)/100 000 person years in the patients (excluding the first year of follow-up: 20.8 [18.8–23.0]), and 16.6 (16.0–17.2) in the reference individuals. The hazard ratio (HR) for pancreatic cancer was increased overall: 1.43 (1.30–1.58), in subtypes (Crohn's disease: 1.44 [1.18–1.74]; ulcerative colitis: 1.35 [1.19–1.53]; IBD unclassified: 1.99 [1.50–2.64]) and especially in IBD patients with primary sclerosing cholangitis: 7.55 (4.94–11.5). Patients and reference individuals with pancreatic cancer did not differ in cancer stage (P = 0.17) or pancreatic cancer mortality (HR 1.07 [0.95–1.21]).

Conclusions: Patients with IBD had an excess risk of pancreatic cancer, in particular patients with primary sclerosing cholangitis. However, the cumulative incidence difference after 20 years was small: 0.05%, that is, one extra pancreatic cancer per 2000 IBD patients.

Introduction

Pancreatic cancer is the seventh leading cause of cancer death worldwide,[1] and both its incidence and mortality are expected to increase.[2] In 2018, the age-standardised incidence rate was 4.8 per 100 000 person years and the mortality rate 4.4. Pancreatic cancer occurs more frequently in men than in women and is more common in industrialised parts of the world, possibly due to lifestyle factors, differences in diagnostic intensity and an older population.[2] Established risk factors for pancreatic cancer include smoking,[3] obesity,[4] chronic pancreatitis,[5,6] diabetes mellitus,[7] non-0 blood type,[8] cystic fibrosis,[9] neoplastic pancreatic cyst,[10] helicobacter pylori infection[11] and hereditary factors.[12,13]

Patients with inflammatory bowel disease (IBD) have an increased risk of intestinal[14–22] and extra-intestinal cancer[14–20,23,24] overall, as well as an increased risk of other pancreatic diseases,[25] such as pancreatitis.[26–30] An increased risk of pancreatic cancer was reported in patients with primary sclerosing cholangitis (PSC) compared to the general population in a study where 79% of the patients with PSC had IBD,[31] and one study found an increased risk of pancreatic cancer in IBD patients with PSC compared to IBD patients without PSC.[32] However, no significant excess risk has been observed in previous population-based studies of pancreatic cancer in patients with IBD compared to the population[15–17,23,24,33,34] (Table S1), except among female patents with Crohn's disease in Korea.[17] However, previous studies on overall cancer risk may have been too underpowered to analyse specific cancers (26 cases of pancreatic cancer found in six studies combined), and no study has specifically investigated the risk of pancreatic cancer in patients with IBD.

To test the hypothesis that IBD patients have an increased risk of pancreatic cancer, we performed a binational register-based cohort study, based on data prospectively recorded in routine clinical practice, with the aim to assess the absolute and relative risks of pancreatic cancer and pancreatic cancer death in patients with IBD compared to the general population.

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