Children with inflammatory bowel disease (IBD) have a greater risk for cancer, especially gastrointestinal cancers, both in childhood and later in life.
New analysis of 9405 children revealed that during follow-up through adulthood, 497 people with childhood-onset IBD had first cancers, resulting in a rate of 3.3 first cancers per 1000 person-years. This compares with a rate of 1.5 per 1000 person-years in the general population.
Ola Olén, MD, PhD, a pediatric gastroenterologist and senior researcher at Sachs’ Children and Youth Hospital, Stockholm South General Hospital, Sweden, and colleagues found that this high cancer risk has not fallen over time and thus does not appear to be affected by currently available therapies.
The investigators used data from a Swedish nationwide database. The large study allowed the investigators to stratify data for calendar period, thus making it possible for them to comment on changes over time. They used International Classification of Diseases codes recorded prospectively in clinical practice as proxies for disease extent and disease behavior. They report their findings online September 21 in BMJ.
The researchers note that their register did not contain information on smoking, nor did they have detailed information on disease severity, disease extent, or disease behavior.
The new results are similar to those documented in a US study of childhood-onset IBD with ulcerative colitis and another of Crohn’s disease with onset before age 22 years.
Risk Factors for Cancer
“Our study confirms reports that primary sclerosing cholangitis is a risk factor for cancer in inflammatory bowel disease,” the authors write. “It adds to previous literature in calculating a precise risk estimate in children with inflammatory bowel disease. More than 700 patients with inflammatory bowel disease in our study had a diagnosis of primary sclerosing cholangitis, which corresponds to 7% of patients with inflammatory bowel disease (11% in ulcerative colitis and 3% in Crohn’s disease).”
In addition, the investigators found that chronic liver disease, longstanding colitis, and a family history of any cancer in relatives younger than 50 years of age were also strong risk factors for any cancer in patients with childhood-onset IBD. Patients had a higher risk for cancer in the first year of follow-up, likely because of improved detection and surveillance.
Type of Cancer
The investigators calculated that gastrointestinal cancer represented 40% of cancers documented in individuals with childhood-onset IBD. The hazard ratio for gastrointestinal cancers was 18.0 (95% confidence interval [CI], 14.4 – 22.7) on the basis of 202 cancers in their cohort of patients with IBD.
When the researchers examined the risk for lymphoid neoplasms in childhood-onset IBD, they found a 2.7-fold increased risk for lymphoid neoplasms (95% CI, 1.7 – 4.2) in patients with childhood-onset IBD. The relative risks for lymphoma were similar in patients diagnosed with ulcerative colitis and Crohn’s disease.
Effect of Treatment
When the investigators stratified the risk for any cancer by medical treatment, they found no clear differences between groups. “We cannot rule out that thiopurines or TNF [tumor necrosis factor] inhibitors increase the risk of cancer, as our study was not big enough to recognise whether drugs are a major risk factor for cancer development in children and young adults,” the authors write. “Instead, we suggest that extent and duration of chronic inflammation might be the main driving mechanisms underlying the increased risk of cancer.”
In an accompanying editorial, Susan Hutfless, PhD, assistant professor of medicine at Johns Hopkins University in Baltimore, Maryland, agrees that the data are not sufficient to make a conclusion about treatments and cancer risk. “We are unable to determine the relation between cancer risk and use of immunomodulators, biological agents, or their combination owing to incomplete information on exposure to infliximab, as well as insufficient follow-up and power,” she explains in the editorial. “The study would require at least five times as many participants (or person years of follow-up) to be powerful enough to detect a doubling of lifetime risk of cancer associated with immunomodulators or biological agents.”
The authors have disclosed no relevant financial relationships. Dr Hutfless reports that AbbVie, Shire, and Janssen pharmaceuticals provide generic educational expenses for trainees in her department.
BMJ. Published online September 20th, 2017. Abstract, Editorial
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