Pediatric-Onset IBD Increases the Risk of Several Cancers

Rahma Elmahdi

Patients with pediatric-onset inflammatory bowel disease (IBD) are at a substantially higher risk of developing liver, colorectal, or other gastrointestinal cancers later in life.

A team, led by Rahma Elmahdi, Center for Molecular Prediction of Inflammatory Bowel Disease, Department of Clinical Medicine, Aalborg University, evaluated the relative risk of cancer for patients with pediatric-onset IBD.

Cancer Rates

IBD has been linked to an increased risk of a number of cancers in adults, including colon, small bowel, and upper gastrointestinal tract cancers.

Rates of IBD are increasing among the pediatric population. However, the long-term risk of cancer in this patient population is not currently known.

“Pediatric patients with IBD may have longer durations of exposure to the chronic inflammatory state and thereby a higher risk of cancer,” the authors wrote. “Furthermore, among children, the incidence of IBD and the risk of cancer have increased in recent years.”

In the past, investigators have found an increase in all-cause cancer among patients with pediatric-onset IBD, but the studies were heterogeneous and limited in size, with variable estimates.

Selecting the Data

In the comprehensive systematic study, the investigators identified all unselected, population-based cohort studies of pediatric-onset IBD assessing the risk of cancer up until October 31, 2021.

Studies focusing on tertiary center referrals or insurance databases were excluded.

The investigators employed a random-effects model meta-analysis of included studies using the inverse-variance method to assess the relative rate of cancer overall and by IBD subtype, sex, and thiopurine exposure among patients with pediatric-onset IBD.

While 4628 articles were screened, only 5 population-based studies from North American and Europe involving 19,812 patients followed up for 283,540 person-years were eligible for inclusion. Of this group, 715 cases of cancer were identified.

The Risk of Cancer

The meta-analyses of pooled relative rate estimates showed a 2.4-fold increase in the rate of cancer among patients with pediatric-onset IBD (pRR, 2.46; 95% CI, 2.06-2.93). The pooled relative rates were 2.03 (95% CI, 1.67-2.46) for patients with Crohn’s disease and 2.61 (95% CI, 2.00-3.40) for patients with ulcerative colitis.

The increased rate was largely because of 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.

This equated to a 55-fold increased rate of liver cancer, a 20-fold increased rate of colorectal cancer, and a 16-fold increased rate of small bowel cancer.

While only 2 studies focused on the relative risk of cancer by sex, the data shows an increased relative rate of cancer among male patients with pediatric-onset IBD (pRR, 3.23; 95% CI, 2.35-4.45) and a nonsignificant increased relative rate for female patients with pediatric-onset IBD (pRR, 2.45; 95% CI, 0.93-6.46) compared with reference populations.

There were also 2 studies that focused on the risk of cancer by treatment exposure. Here, they found an increased relative rate of cancer among patients treated with thiopurines (pRR, 2.09; 95% CI, 1.55-2.83), but the relative rate of cancer among patients not exposed to thiopurines was numerically but not statistically increased (pRR, 1.82; 95% CI, 0.63-5.22).

In addition, the incidence rate of cancer in this patient population ranged from 1.0-3.3 cases per 1000 person-years in the 4 selected studies.

“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,” the authors wrote.

The study, “Development of Cancer Among Patients With Pediatric-Onset Inflammatory Bowel Disease,” was published online in JAMA Network Open.