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

Abstract

Objective To assess risk of cancer in patients with childhood onset inflammatory bowel disease in childhood and adulthood.Design Cohort study with matched general population reference individuals using multivariable Cox regression to estimate hazard ratios.Setting Swedish national patient register (both inpatient and non-primary outpatient care) 1964-2014.Participants Incident cases of childhood onset (<18 years) inflammatory bowel disease (n=9405: ulcerative colitis, n=4648; Crohn's disease, n=3768; unclassified, n=989) compared with 92 870 comparators from the general population matched for sex, age, birth year, and county.Main outcome measures Any cancer and cancer types according to the Swedish Cancer Register.Results During follow-up through adulthood (median age at end of follow-up 27 years), 497 (3.3 per 1000 person years) people with childhood onset inflammatory bowel disease had first cancers, compared with 2256 (1.5 per 1000 person years) in the general population comparators (hazard ratio 2.2, 95% confidence interval 2.0 to 2.5). Hazard ratios for any cancer were 2.6 in ulcerative colitis (2.3 to 3.0) and 1.7 in Crohn's disease (1.5 to 2.1). Patients also had an increased risk of cancer before their 18th birthday (2.7, 1.6 to 4.4; 20 cancers in 9405 patients, 0.6 per1000 person years). Gastrointestinal cancers had the highest relative risks, with a hazard ratio of 18.0 (14.4 to 22.7) corresponding to 202 cancers in patients with inflammatory bowel disease. The increased risk of cancer (before 25th birthday) was similar over time (1964-1989: 1.6, 1.0 to 2.4; 1990-2001: 2.3, 1.5 to 3.3); 2002-06: 2.9, 1.9 to 4.2; 2007-14: 2.2, 1.1 to 4.2).Conclusion Childhood onset inflammatory bowel disease is associated with an increased risk of any cancer, especially gastrointestinal cancers, both in childhood and later in life. The higher risk of cancer has not fallen over time.

Fig 1 Comparison of age at first visit or admission to hospital listing a diagnosis of inflammatory bowel disease between cohorts with onset in 1964-2001 and 2002-14. IBD=inflammatory bowel disease.

Fig 2 Adjusted* hazard ratios for all cancers during all available follow-up in patients with childhood onset (<18 years) inflammatory bowel disease and matched general population comparators in 1964-2014 (first year of follow-up included). Numbers in the figure represent cancers in patients with inflammatory bowel disease, and forest plots represent hazard ratio (95% confidence interval). Follow-up of extra-intestinal manifestations, primary sclerosing cholangitis, colitis during follow-up, and surgery started at the first date of the corresponding register entry. Follow-up of colitis ≥10 years before start of follow up started 10 years after the first diagnostic listing of colitis. *For sex, age at diagnosis, calendar year at diagnosis, and county.

Fig 3 Kaplan-Meier cumulative incidence curves with 95% confidence intervals showing the proportion of patients at risk of cancer after index date by calendar period of onset. The numbers show the number at risk (top) and the number of events since the previous data point (bottom) by inflammatory bowel disease status. IBD=inflammatory bowel disease.

Fig 4 Adjusted† hazard ratios of first ever event of a cancer in the cohort of patients with childhood onset (<18 year) inflammatory bowel disease during all available follow-up, compared with matched reference individuals from the general population (1964-2014), including first year of follow-up. Numbers next to the forest plot represent the number of cancers in patients with inflammatory bowel disease, hazard ratios, and 95% confidence intervals. *Other cancers are all cancer types not listed separately. †For sex, age at diagnosis, calendar year at diagnosis, and county

Fig 5 Adjusted* hazard ratios for all cancer occurring before the 18th birthday in patients with childhood onset (<18 years) inflammatory bowel disease and matched general population comparators 1964-2014 (first year of follow-up included). Numbers next to the forest plot represent the number of cancers in patients with inflammatory bowel disease, hazard ratios, and 95% confidence intervals. Follow-up of extra-intestinal manifestations, primary sclerosing cholangitis, colitis during follow-up, and surgery started at the first date of the corresponding register entry. Follow-up of colitis ≥10 years before start of follow up started 10 years after the first diagnostic listing of colitis. *For sex, age at diagnosis, calendar year at diagnosis, and county.