Although persistent inflammation has long been associated with colon cancer in patients with ulcerative colitis, a large, carefully controlled University of Chicago study has confirmed the link between the severity and duration of inflammation and increased colorectal cancer risk.
But it also showed that treatment with immune modulators significantly decreased that risk. And that male colitis patients are at higher risk for colorectal cancers.
Building on their results, the researchers propose the development of “new stratified surveillance and treatment strategies” to prevent and detect cancer in these patients.
“Our study provides strong evidence of a protective effect of immunomodulators against ulcerative colitis-associated colorectal neoplasia,” said study director David Rubin, MD, professor of medicine at the University of Chicago. “The mechanism of such an interaction, however, is unknown. More work is needed in this area.”
In their paper, published early online in Clinical Gastroenterology and Hepatology, the researchers evaluated 200 ulcerative colitis patients followed at the University of Chicago Medicine between 1994 and 2005. They compared 59 patients who developed colorectal cancer or dysplasia with 141 who did not.
The study was unique in several important ways, the authors point out. They controlled for age, family history, smoking and medications, as well as the extent, severity and duration of disease.
They developed a new six-point scale to measure inflammatory activity and applied it to tissue from 4,449 biopsies specimens obtained in 335 procedures. Normal tissue was labeled as 0, tissue with quiescent disease 1.
Ratings went up to 5, denoting abscesses in more than 50 percent of crypts, erosion or ulceration. They even had two pathologists review many of the sample tissues to confirm consistent assessment.
The key finding was the significant reduction in cancer risk among patients who received anti-inflammatory drugs, such as mesalamine. Adjusting for other factors, use of anti-inflammatories decreased risk of colorectal cancer by an estimated 37 percent.
“This tells us that we need to stratify patients for cancer risk in a new way,” Rubin said. “We need to shift the focus from episodic control of symptoms to sustained control of inflammation, with a particular emphasis on intensive surveillance strategies for those at highest risk.”
Funding for this study came from Warner Chilcott (formerly Proctor and Gamble Pharmaceuticals), the Digestive Disease Research Core Center of the University of Chicago, the National Institute of Diabetes and Digestive and Kidney Diseases, and the Cancer Research Foundation on Chicago.
Additional authors were Dezheng Huo, Jami Kinnucan, Mina Sedrak, Nicole McCullom, Alana Bunnag, Elin Raun-Royer, Russell Cohen, Stephen Hanauer, John Hart and Jerrold Turner, all of the University of Chicago Medicine.