Children who had developed inflammatory bowel disease had an 18-fold greater risk of gastrointestinal cancers in later life, a new study suggests.

The cohort study found that the risk of all cancers was elevated in individuals with childhood-onset inflammatory bowel disease, but particularly in those with primary sclerosing cholangitis and ulcerative colitis.

Researchers followed 9,405 patients with childhood-onset inflammatory bowel disease to a mean age of 27 years using a Swedish national patient register ( BMJ. 2017 Sep 21. doi: 10.1136/bmj.j3951 ).

Analysis revealed that individuals with childhood-onset inflammatory bowel disease had double the risk of any cancer, compared with the general population (hazard ratio, 2.2; 95% confidence interval, 2.0-2.5), and a 2.7-fold greater risk of developing cancer before the age of 18 years.

Primary sclerosing cholangitis was associated with a sixfold greater risk of cancer, ulcerative colitis was associated with a 2.6-fold greater risk, and patients who had had colitis for 10 years or more had a nearly fourfold greater risk of cancer (HR, 3.9).

The study also found that childhood-onset inflammatory bowel disease was associated with an 18-fold greater risk of gastrointestinal cancer, compared with the general population, matched for age, sex, birth year, and county.

The risk was particularly high in patients with ulcerative colitis, who showed a 33-fold higher risk of colorectal cancer, while patients with Crohn’s disease had a nearly 6-fold higher risk.

“Colorectal cancer is a major cause of cancer mortality in the population, and even a moderately increased incidence is likely to have a large effect on patients with inflammatory bowel disease,” wrote Ola Olén, MD, of Karolinska Institutet, Stockholm, and coauthors.

When the researchers looked in more detail at the type of cancers, they saw the greatest increases in risk were for colorectal cancer (HR, 19.5) and small intestinal cancer (HR, 12.8), while the risk of liver cancer was 134 times higher (95% CI, 59.6-382).

The researchers also saw a 2.7-fold increased risk of lymphoid neoplasms associated with childhood inflammatory bowel disease, particularly in individuals with ulcerative colitis or Crohn’s disease. The most common lymphoid neoplasms were non-Hodgkin lymphomas, followed by Hodgkin lymphomas.

Commenting on possible explanations for the associations seen in the study, the authors said that patients with inflammatory bowel disease may have their gastrointestinal cancers diagnosed earlier than the general population because of regular endoscopies.

They also said that thiopurines and TNF inhibitors – both used to treat inflammatory bowel disease – could not be ruled out as a possible cause of the increase in cancer risk, but their study was not powered to pick up such an effect.

“Instead, we suggest that extent and duration of chronic inflammation might be the main driving mechanisms underlying the increased risk of cancer,” they wrote.

The authors noted that their study did not include data on the smoking status of individuals, which could be significant, because smoking is known to reduce the risk of ulcerative colitis and increase the risk of Crohn’s disease and cancer. However, they pointed out that the majority of patients would not have been smoking at the time of their initial inflammatory bowel disease diagnosis, and would have been unlikely to take up the habit after their diagnosis.

With the observation that the risk of cancer in inflammatory bowel disease was higher in patients who were younger when diagnosed with the disease, the authors suggested that age of onset be considered when designing surveillance strategies for cancer in this group.

The Stockholm County Council and the Karolinska Institutet, the Swedish Cancer Society, the Swedish Research Council, and the Swedish Foundation for Strategic Research supported the study. One author received grants from the Swedish Medical Society, Magtarmfonden, the Jane and Dan Olsson Foundation, the Mjölkdroppen Foundation, the Bengt Ihre Research Fellowship in gastroenterology, and the Karolinska Institutet Foundations. No conflicts of interest were declared.


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