A new study of people living in Sweden has found that children with inflammatory bowel disease have a higher risk of cancer – especially gastrointestinal cancers – both in childhood and in later life, compared with individuals without the disease.
The international team of researchers, including members of the Karolinska Institutet in Sweden, report the findings in the BMJ.
They note that the raised risk of cancer for children with inflammatory bowel disease (IBD) carries on into adulthood and has not reduced following the introduction of new ways to manage the disease, such as with biological agents.
They also point out that, while they found a higher relative risk of cancer, the absolute risks are low. Compared with healthy individuals, there was one extra case of cancer for every 556 people with IBD followed for 1 year.
IBD results from chronic inflammation of the gut, or gastrointestinal (GI) tract. It can strike at any age, but most people who are diagnosed are between 15 and 40 years old.
For example, in Crohn’s disease, the inflammation affects any region of the GI tract between the mouth and the anus and can occur in all layers of the tissue. In ulcerative colitis, however, the disease affects the colon and the rectum and tends only to occur in the innermost layer of tissue.
IBD is classed as an autoimmune disorder – that is, a disease that arises when the immune system mistakenly attacks the body’s own tissue: in this case, the gut.
The exact causes of IBD are still unknown, but scientists suggest that environmental factors might trigger the disease in people whose genetic makeup makes them more susceptible to it.
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In their study paper, the researchers explain that while a number of studies have identified a link between IBD and a higher risk of cancer, few have examined lifetime cancer risk of IBD that starts in childhood, and those that do “lack details of absolute and relative risks.”
For their investigation, the team used data from a nationwide register of people living in Sweden. They compared cancer rates in people with childhood-onset IBD – which is diagnosed before the age of 18 – to rates of cancer in the general population.
Their analysis included 9,405 people with childhood-onset IBD and 92,870 individuals from the general population matched for birth year, age, sex, and place of residence.
The researchers calculated the risk of cancer in the two groups before the age of 18, before age 25, and over the whole study period – from 1964 to 2014 – up to an average age of 30 years.
After excluding the effect of other factors that might influence the result, the team found 497 first cancers in people with childhood-onset IBD, which is equivalent to a rate of 3.3 per 1,000 person-years. This compared with 2,256 cancers in the matched individuals, which is equivalent to 1.5 per 1,000 person-years.
“This corresponds to one extra case of cancer for every 556 patients with inflammatory bowel disease followed for a year, compared with reference individuals,” they note.
The team also found that the cancer risk increased in the first year following IBD diagnosis and stayed high over 5 years of follow-up and beyond. This was especially the case for cancers of the colon, rectum, small intestine, and liver.
Risk factors for any cancer linked to childhood-onset IBD included long-standing colitis, chronic liver disease, and a family history of early-onset cancer.
The authors note that they do not rule out that drugs may be a factor in the higher risk of cancer in childhood-onset IBD, but they explain that their study was “not big enough” to assess this.
However, they do suggest that the main driver underlying the higher risk of cancer could be the “extent and duration of chronic inflammation” of the IBD.
They also emphasize that because this was an observational study, it could not determine whether IBD causes cancer.
Nevertheless, the researchers suggest that the study’s biggest strength is the large number of participants. They also outline some weaknesses, such as the fact that they had no information about smoking or about “disease severity, disease extent, or disease behavior.”
They conclude, “Childhood-onset inflammatory bowel disease is associated with an increased risk of any cancer, especially gastrointestinal cancers, both during childhood and later in life. The higher risk of cancer has not fallen over time.”
In a linked editorial, Susan Hutfless – who is an associate professor of medicine at Johns Hopkins University in Baltimore, MD – acknowledges that people with IBD “worry about developing cancer,” but she urges them and their families “to focus on the very low incidence of cancer in childhood.”
The study “sets an excellent example” of how to investigate the link between IBD and cancer, Prof. Hutfless notes. However, she points out that only very much larger studies can address questions such as whether IBD drugs raise cancer risk, and the best way to go about cancer surveillance in patients with IBD.
She describes the study as a “thoughtful and thorough investigation” and says that it “confirms the need for international collaboration in the study of cancer surveillance” for children diagnosed with IBD.
As the investigators themselves point out, Prof. Hutfless notes that better surveillance of IBD could lead to better detection, earlier diagnosis, and higher reported rates of cancer. “The ultimate goal of surveillance,” she adds, “is of course reduced cancer mortality, an outcome that requires very long follow-up.
“Children and their families worrying about cancer risks today might have a long time to wait for reliable information about the long-term effects of different treatments.”
Prof. Susan Hutfless