Children with IBD face increased subsequent cancer risk

Paediatric-onset inflammatory bowel disease (IBD) carries a doubled risk of developing cancer later in life, with skin, lymphoid, and gastrointestinal tumours of a particular concern, a study has found. The risk is higher in males and independent of IBD subtype and medical treatment.

“Notably, our observation of a twofold increased risk of cancer in patients with paediatric-onset IBD, which may cause unnecessary concern, corresponded to only one additional case of cancer for every 1,000 individuals followed for a year,” according to researchers, adding that absolute rather than relative risk estimates should inform management guidelines.

The analysis used data from the Danish National Patient Registry and included 5,380 paediatric IBD patients (Crohn’s disease, n=2,673; ulcerative colitis, n=2,707) who were followed for 77,821 person-years. Each patient was matched by sex and age to 10 non-IBD controls selected from the general population.

Over a median follow-up of 12 years, 158 paediatric IBD patients and 701 controls developed cancer. The corresponding incidence rates were 2.03 and 1.00 per 1,000 person-years. Those with paediatric-onset IBD were twice as likely to develop cancer (hazard ratio [HR], 2.16, 95 percent confidence interval [CI], 1.82–2.58), according to multivariable Cox proportional hazards regression analyses. [Gastroenterology 2020;doi:10.1053/j.gastro.2020.06.030]

The overall risk increase was driven by a rise in the risks of liver (HR, 22.68, 95 percent CI, 8.51–63.15), colorectal (HR, 17.22, 95 percent CI, 9.05–32.75) and small bowel cancers (HR, 4.58, 95 percent CI, 1.82–11.45), lymphoid cancer (HR, 2.43, 95 percent CI, 1.28- 4.62), and melanoma (HR, 2.01, 95 percent CI, 1.19–3.42) and non-melanoma skin cancers (HR, 2.21, 95 percent CI, 1.49–3.28).

Further analyses indicated that the association between IBD and increased cancer risk was more pronounced among male than female patients (HRs, 3.89 and 1.49; p<0.001), observed in both IBD subtypes (Crohn’s disease: HR, 2.25, 95 percent CI, 1.75–2.89; ulcerative colitis: HR, 2.09, 95 percent CI, 1.64–2.66), and similar in patients who had (HR, 2.28, 95 percent CI, 1.17-4.46) and had not undergone colectomy (HR, 2.16, 95 percent CI, 1.80–2.58).

Cancer risk was not modified by age, year of diagnosis, and medical treatment.

The observations are in line with a Swedish nationwide cohort study. A recent multicentre study of a similar population of patients, although not exclusively population-based, also described a risk increase in some but not all the 25 included countries. [BMJ 2017;358:j3951; Aliment Pharmacol Ther 2018;48:523-537]

“The increased risk of cancer in the present study was explained by [heightened] risk of skin, lymphoid, and gastrointestinal cancer, confirming results from the Swedish cohort study,” the researchers said.

“Chronic inflammation in IBD may promote carcinogenesis due to rapid regeneration of cells, especially in patients diagnosed early in life. Yet, the long-term risk of cancer in paediatric-onset IBD, particularly in the context of immunomodulatory treatment remains debated,” they noted. [Gastroenterology 2017;152:1901-1914; JAMA 2014;311:2406-2413; BMJ 2017;358:j3951; Aliment Pharmacol Ther 2018;48:523-537; Am J Gastroenterol 2013;108:1647-1653]

The researchers advised that the findings be considered in light of potential study limitations. “Inclusion was based on two separate registrations with IBD to decrease the likelihood of misdiagnosis, yet potential inclusion of false positive cases may bias findings towards the null. We did not have data at the national level describing disease severity or smoking habits.”