Colorectal cancer in ulcerative colitis: a cohort study of primary referrals from three centres.

Abstract

SUMMARY A retrospective cohort of 823 patients with ulcerative colitis who resided at the time of diagnosis in one of three defined geographical areas (West Midlands region, Oxford region, England and Stockholm County, Sweden) was assembled. The patients were first seen at named hospitals in these areas and the diagnosis of ulcerative colitis established within five years of onset of symptoms between 1945-1965. All patients were 15 years of age or more at onset of disease and were followed for a minimum of 17 years and a maximum of 38 years. Ninety seven per cent completeness of follow up was achieved. Examining the colorectal cancer risk in the series relative to the risk in the general population by standardised morbidity ratios, there was an eight fold increased risk of cancer in the series as a whole. Dividing the series by extent of colitis, extensive colitis patients showed a 19 fold increase in risk. A four fold increased risk was shown in the remainder of the series (left sided colitis, proctitis and extent unknown). Life table analyses in extensive colitis gave cumulative risks of 7*2% (CI 3-6-10-8) at 20 years from onset of disease and 16-5% (CI 9.0-24.0) at 30 years from onset. No significant effect of age at onset, sex or referral centre could be detected. Examination of the data by interval from onset to cancer and by actual age at development of cancer suggests that patients who develop colorectal cancer will do so in a distribution around 50 years of age independent of duration of disease in adult onset ulcerative colitis (>15 years at onset of disease). An inverse relationship was shown between age at onset of disease and interval from onset of disease to cancer. Further age specific rates for cancer increased up to 50 years and decreased thereafter. These results suggest that extensive colitis patients have a genetic predisposition to colorectal cancer and that longstanding inflammation is not of prinwary importance in the initiation/promotion of cancer in this disease.There is convincing evidence from previous studies more likely to be the result of selection biases that patients with ulcerative colitis have a higher inherent in these series rather than any real differincidence of colorectal cancer than the general ences in the underlying cancer incidence of the population.' This increased incidence occurs pre-groups under review. dominantly in patients with longstanding extensive colitis. Many previous estimates of the colorectal Methods cancer incidence have been based on information drawn from hospital series of patients (Table 1) groups of patients are only found in hospitals special-

Predominant T helper type 2‐inflammatory responses promote murine colon cancers

“…3). 3 Differences from all other experimental groups were statistically significant (p < 0.02).- 4 Differences from WT mice with AOM or AOM1TNBS were statistically significant (p<0.02).- 5 Difference from IL-4 2/2 mice treated AOM was statistically significant (p < 0.02). …”

“…1 Of note, patients with longstanding, extensive UC have a high cancer risk,~16.5% at 30 years, after initial diagnosis. 2,3 It has long been noted that cancer arises from regions of chronic inflammation, and the inflammatory cells and cytokines of the immune system found in tumors are more likely to contribute to tumor growth and progression. 4 In animal models, colitis induced by dextran sulfate sodium (DSS) are associated with dysplasia and cancer.…”

Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopreventive agent curcumin involves inhibition of NF-κB activation via the NIK/IKK signalling complex

“…The lumenal concentration of TNFa is increased in patients with in¯ammatory bowel disease (Braegger et al, 1992), a condition which predisposes to colorectal cancer (Gyde et al, 1998). Fecapentaene-12, the most abundant form of a group of mutagenic chemicals found in the faeces of individuals who consume a Western diet high in fat and meat (Schi man et al, 1989), has been shown to be a tumour promotor in a rat model of colorectal cancer (Zarcovic et al, 1993).…”

Current overview of colitis-associated colorectal cancer

“…It was revealed that IBD patients with proctitis and proctosigmoiditis are at the lowest risk of CACRC and the higher risk is combined with left-sided colitis and pan-colitis [15,16].…”