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OP024 Childhood-onset inflammatory bowel disease and risk of cancer – a Swedish nationwide cohort study 1964–2014

Olén O.*1,2, Askling J.1, Frumento P.3, Sachs M.C.3, Neovius M.1, Eriksson J.1, Smedby K.E.1, Ekbom A.1, Malmborg P.1,2, Ludvigsson J.F.4,5,6,7

1Karolinska Institutet, Department of Medicine Solna, Clinical Epidemiology Unit, Stockholm, Sweden 2Sachs' Children's Hospital, Department of Pediatric Gastroenterology and Nutrition, Stockholm, Sweden 3Karolinska Institutet, Institute of Environmental Medicine, Stockholm, Sweden 4Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Stockholm, Sweden 5Orebro University Hospital, Department of pediatrics, Orebro, Sweden 6University of Nottingham, Division of Epidemiology and Public Health, School of Medicine, Nottingham, United Kingdom 7Columbia University College of Physicians and Surgeons, Department of Medicine, New York, Sweden

Background

Inflammatory bowel disease (IBD) with onset in adult age has been linked to an increased risk of cancer, especially colorectal cancer, but risk assessments in childhood-onset IBD are scarce.

Methods

We used Cox regression to estimate hazard ratios (HRs) for cancer in 9,341 individuals with childhood-onset IBD (<18 years) (ulcerative colitis (UC): n=3,380; Crohn's disease (CD): n=3,046; IBD-unclassified (IBD-U): n=2,915) compared to 92,224 general population comparators matched for sex, age, year, and place of residence. Data on incident cases of IBD 1964–2014 were obtained from the National Swedish Patient Register comprising both inpatient- and non-primary outpatient care, while cancer data were obtained through the Swedish Cancer Register. Medication data was obtained from the National Prescribed Drug Register for incident cases of childhood onset IBD since 2005 (n=3,386).

Results

There were 509 (3.46/1000 person-years) first cancers in patients with childhood-onset IBD compared to 2,237 (1.52/1000 person-years) in the general population comparators during follow-up, corresponding to a HR of 2.30 (95% confidence Interval (CI)=2.09–2.53). HRs for any cancer were 3.19 in UC and 1.76 in CD. While the relative risk was highest the first year of follow-up (HR=6.03), it remained elevated also after ≥5 years of follow-up (HR=2.29; 95% CI: 2.07–2.53). Patients with childhood-onset IBD also had an increased risk of cancer before their 18th birthday (HR=3.54; 95% CI: 2.22–5.46, n=26 cancers in IBD). Gastrointestinal cancers were associated with the highest relative risks (<18th birthday: HR=40 (95% CI: 13–175, n=12 cancers in IBD); ≥18th birthday: HR=18 (95% CI: 14–23, n=194 cancers in IBD)), but the absolute risks were low.

Figure 1. Hazard ratio of cancer in childhood-onset IBD, as compared to matched general population reference individuals 1964–2014. Numbers next to the forest plot represent the number of cancers in IBD-patients, Hazard ratio (95% confidence interval).

Patients with exposure to thiopurines (HR=4.23; 95% CI: 2.14–7.91) did not have a significantly more increased risk of cancer than patients never exposed to thiopurines (HR=3.59; 95% CI: 1.5–7.71).

Conclusion

Childhood-onset IBD is associated with an increased risk of cancer, both during childhood and later in life, especially gastrointestinal cancer. Thiopurine treatment in children is unlikely to be a major risk factor for cancer development in IBD in this age group