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IBD-related cancer risks attributed to chronic inflammation, immunosuppressive drugs
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The risk for a variety of cancers in patients with inflammatory bowel disease can be linked to chronic intestinal inflammation or immunosuppressive therapies, according to findings in a recently published review article.
“Among the chronic inflammatory diseases that often require the prolonged use of immunosuppressants, [IBD] is an intriguing model because immunosuppressants may reduce the incidence of inflammation-related cancers through their anti-inflammatory effects or promote immunosuppression-related cancers,” wrote Laurent Beaugerie, MD, PhD, from Hôpital Saint-Antoine in Paris, and Steven H. Itzkowitz, MD, from Icahn School of Medicine at Mount Sinai.
Laurent Beaugerie
Colorectal cancer
Compared with the general population, patients with IBD have a 1.5- to twofold increased risk for colorectal cancer in North America and some European countries, and teenagers with pancolitis have more than a 15% lifetime risk, the authors wrote. However, a gradual decrease in excess risk for colorectal cancers in patients with IBD has been observed in some studies, which one meta-analysis “attributed to better control of inflammation, better implementation of colonoscopic surveillance, increased implementation of colectomy in some countries, and the possible chemopreventive effective of 5-aminosalicylates (5-ASAs).”
Factors that increase risk for colorectal cancer specifically in patients with IBD include:
- primary sclerosing cholangitis;
- cumulative increase in colonic inflammatory lesions;
- increasing IBD duration;
- active chronic inflammation as determined by endoscopy or histology;
- anatomical abnormalities such as foreshortened colon, strictures and pseudopolyps; and
- history of flat dysplasia.
Up to 15% of colorectal cancers are diagnosed within the first 7 years of IBD onset, and it is a point of controversy whether young age at IBD diagnosis is a risk factor independent from duration of IBD.
Chronic inflammation is an assumed cause of colitis-related cancer, whereas the impact of altered luminal microbiota is currently “the subject of intense research.”
Surveillance colonoscopy in patients with IBD is made difficult by the presence of strictures, actively inflamed mucosa and inflammatory pseudopolyps, and colitis-associated dysplastic lesions are difficult to detect endoscopically due to their flatness and less distinctive borders.
Although 5-ASAs, thiopurines and tumor necrosis factor-alpha antagonists are potentially chemopreventive, studies testing this have produced conflicting results, and such trials are difficult to perform.
Small bowel adenocarcinoma
Patients with Crohn’s disease have a 20- to 30-fold increased risk for small bowel adenocarcinoma compared with non-Crohn’s patients, and it typically occurs in ileal lesions more than 8 years after Crohn’s diagnosis.
Surgical excision of ileal lesions is the only preventive technique currently available. Endoscopic surveillance for high-risk patients “is problematic because extensive and stricturing lesions make ileoscopy for the full visualization of the segments of the small bowel affected by Crohn’s disease difficult or impossible,” the authors wrote.
Intestinal lymphomas, anal cancers and cholangiocarcinoma
Patients with IBD have a higher risk for primary intestinal lymphomas, but the absolute risk is low at 0.1 per 1,000 patient-years. These are typically B-cell non-Hodgkin’s lymphomas occurring in middle-aged males after 8 years of Crohn’s diagnosis.
Annual incidence of anal squamous cell carcinoma in patients with IBD is comparable to the general population at 0.01 to 0.02 per 1,000 person-years. The incidence rate of anal cancers occurring in the fistulae of patients with long-standing fistulizing perianal CD is 0.2 per 1,000 patient-years, and diagnosis can be delayed due to “nonspecific clinical presentation and because access to lesions is difficult in the presence of stenosis.” Patients with fistula-associated cancers have overall poor prognosis.
The risk for cholangiocarcinoma in patients with IBD is two to four times higher compared with the general population, but absolute risk is low at 0.08 per 1,000 person-years. IBD patients with primary sclerosing cholangitis account for most of this risk, with 5% to 10% lifetime risk and a 160-fold increased risk compared with the general population. Prognosis is poor despite annual imaging and serum testing strategies.
Other IBD-associated cancers
Patients with IBD may have a higher risk for a variety of other cancers due to long-term exposure to immunosuppressants, including non-Hodgkin’s lymphoma, other types of lymphoproliferation more rarely, acute myeloid leukemia, severe myelodysplastic syndromes, nonmelanoma and melanoma skin cancers, HPV-related cervical cancer and urinary tract cancers.
Current use of thiopurines for IBD has been shown to be associated with an overall RR of cancer of 1.3 to 1.7, which is reversible after withdrawal. No overall excess risk for TNF-a antagonists has been demonstrated, but long-term risks are unknown due to the relatively recent use of biologics. – by Adam Leitenberger
Disclosure: The researchers report no relevant financial disclosures.
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