Development of Cancer Among Patients With Pediatric-Onset Inflammatory Bowel Disease: A Meta-analysis of Population-Based Studies

IMPORTANCE: Because the incidence of pediatric-onset inflammatory bowel disease (IBD) is increasing, knowledge of the long-term risk of cancer in this patient population is required. OBJECTIVE: To evaluate the relative rate of cancer among patients with pediatric-onset IBD. DATA SOURCES: A comprehensive systematic search was performed of MEDLINE and Embase from the date of database inception to October 31, 2021. STUDY SELECTION: All unselected, population-based cohort studies of pediatric-onset IBD assessing the risk of cancer were included. Tertiary center referrals and insurance database studies were excluded. All articles were assessed by 2 independent reviewers. DATA EXTRACTION AND SYNTHESIS: The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline for data extraction and used the Newcastle-Ottawa Scale for assessment of the risk of bias and the quality of included articles. MAIN OUTCOMES AND MEASURES: A random-effects model meta-analysis was conducted of included studies using the inverse-variance method to assess the relative rate of cancer overall and by IBD subtype (Crohn disease or ulcerative colitis), sex, and thiopurine exposure among patients with pediatric-onset IBD. Pooled relative rates (pRRs) along with 95% CIs were calculated for combined studies. RESULTS: Of 4628 articles screened, 5 population-based studies from North America and Europe were eligible for inclusion. These studies comprised 19 812 individuals with pediatric-onset IBD followed up for 283 540 person-years in which 715 cases of cancer were identified. Meta-analysis of pRR estimates showed a 2.4-fold increased rate of cancer among patients with pediatric-onset IBD (pRR, 2.46; 95% CI, 2.06-2.93), seen among patients with Crohn disease (pRR, 2.03; 95% CI, 1.67-2.46) and those with ulcerative colitis (pRR, 2.61; 95% CI, 2.00-3.40). This increased rate is primarily due to an increased rate of liver (pRR, 55.45; 95% CI, 19.59-156.99), colorectal (pRR, 20.29; 95% CI, 15.90-25.90), and small bowel (pRR, 16.20; 95% CI, 3.52-74.66) cancers. The incidence rate of cancer among patients with pediatric-onset IBD was reported by 4 studies and ranged from 1.0 to 3.3 cases per 1000 person-years. CONCLUSIONS AND RELEVANCE: This meta-analysis of unselected, population-based studies showed a greater than 2-fold increased rate of cancer among patients with pediatric-onset IBD compared with the general pediatric populations, primarily owing to an increased rate of gastrointestinal cancers.