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Cancer risk doubled in childhood-onset IBD
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Children with inflammatory bowel disease showed a twofold higher risk for developing cancer, especially GI cancer, and this risk persisted well into adulthood, according to the results of a national cohort study in Sweden.
However, investigators noted that the absolute cancer risk remains low, affecting just one additional IBD patient for every 556 followed per year compared with healthy controls. Further, they found that this increased cancer risk has not fallen since the introduction of immunomodulators and biologic therapies for IBD.
While it is known that patients with IBD show a higher risk for cancer, data on lifetime cancer risks associated with childhood-onset IBD are lacking. Therefore, Jonas F. Ludvigsson, MD, a pediatrician and professor of epidemiology at Karolinska Institutet in Stockholm, Sweden, and colleagues used national registry data spanning 1964-2014 to compare cancer risk in 9,405 individuals diagnosed with IBD before age 18 (49% ulcerative colitis, 41% Crohn’s disease, 11% unclassified) and 92,870 healthy controls from the general population, who were matched by sex, age, birth year and county of residence.
Median follow-up extended to age 27, throughout which 497 patients with IBD received a primary cancer diagnosis compared with 2,256 controls, corresponding to 3.3 vs. 1.5 cases per 1,000 person-years of follow-up (HR = 2.2; 95% CI, 2-2.5). Patients with ulcerative colitis showed a higher relative risk (HR = 2.6; 95% CI, 2.3-3) than those with Crohn’s disease (HR = 1.7; 95% CI, 1.5-2.1).
The risk was also increased in childhood, with 20 cancers occurring among IBD patients before age 18, corresponding to 0.6 cases per 1,000 person-years of follow-up (HR = 2.7; 95% CI, 1.6-4.4).
“Relative risks were increased in the first year after diagnosis ... and remained statistically significantly higher at 5 years of follow-up and onwards,” investigators wrote.
Patients with IBD were most at risk for GI cancer, with 202 cases occurring throughout the follow-up period (HR = 18; 95% CI, 14.4-22.7). These included colorectal cancer, small intestinal cancer and liver cancer. These patients also showed an increased risk for lymphoid neoplasms (HR = 2.7; 95% CI, 1.7-4.2), and both melanoma (HR = 1.7; 95% CI, 1.2-2.4) and non-melanoma skin cancer (HR = 5.9; 95% CI, 3.6-9.5).
Strong risk factors for developing any cancer in those with IBD included primary sclerosing cholangitis, longstanding colitis and family history of cancer in relatives diagnosed younger than age 50.
Finally, the investigators found that the increased cancer risk in patients with IBD has persisted over time, with similar hazard ratios from 1964-1989 (HR = 1.6; 95% CI, 1-2.4), 1990-2001 (HR = 2.3; 95% CI, 1.5-3.3), 2002-2006 (HR = 2.9; 95% CI, 1.9-4.2) and 2007-2014 (HR = 2.2; 95% CI, 1.1-4.2).
“We cannot rule out that thiopurines or TNF inhibitors increase the risk of cancer, as our study was not big enough to recognize whether drugs are a major risk factor for cancer development in children and young adults,” Ludvigsson and colleagues wrote. “Instead, we suggest that extent and duration of chronic inflammation might be the main driving mechanisms underlying the increased risk of cancer.”
While the researchers cautioned that these findings are associations and not causal relationships due to the study’s observational design, they concluded that childhood-onset IBD is linked to an increased risk for cancer, especially GI cancer and lymphoid neoplasms, in both childhood and later in life.
“Relative rates of cancer diagnosed before the 18th birthday were higher for gastrointestinal and hematological cancers but not other cancers,” Susan Hutfless, PhD, of the GI Epidemiology Research Center at Johns Hopkins University, wrote in an accompanying editorial. “The relative rate of female genital cancer at any age did not differ from controls despite previous evidence that women with [IBD] have higher rates of cervical dysplasia than those without.”
Noting that the design of this study is exemplary, she concluded that further research should be performed to confirm these findings, which will help to guide decision-making regarding treatment and surveillance for children with IBD. – by Adam Leitenberger
Disclosures: Hutfless reports that AbbVie, Shire and Janssen provide generic educational expenses for trainees in her department.
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