The continuing uncertainty about cancer risk in inflammatory bowel disease

An increased risk of colorectal cancer (CRC) among individuals with IBD was suggested in the 1920s and later supported by epidemiologic studies.1 The association between IBD and CRC is not thought to arise from shared risk factors,2 but rather from a causal effect of IBD on CRC through chronic inflammation and other mechanisms that promote malignant transformation of the colonic mucosa.3 As a result, patients with IBD are considered at high risk of CRC and therefore receive anti-inflammatory treatment, colonoscopic surveillance with biopsies and prophylactic colectomy. Multiple reviews and meta-analyses have tried to estimate CRC risk in patients with IBD (see table 1 for a summary from six such analyses4–9) and several additional studies were published during the last year.10–13 Few of these studies are large, prospective, population-based studies, which reflect the substantial methodological challenges. Here, we first outline the criteria for valid studies on IBD and cancer and then use those criteria to critically review the existing studies. View this table: Table 1 Summary of meta-analyses of the association between IBD, UC and Crohn's disease (CD) and risk of colorectal cancer (CRC) ### Defining disease onset Failure to accurately ascertain the onset of IBD may bias the effect estimates of IBD on cancer if increasing duration of disease increases the probability of somatic mutations that lead to malignant transformation. However, IBD may only be detected years after onset during colonoscopy screening14 or after early symptoms of CRC. As a result, the relative risk of CRC may be overestimated. Unfortunately, the identification of IBD onset in existing population-based registers is challenging. Its replacement by first hospitalisation due to IBD may misclassify disease onset because outpatient management may suffice until exacerbations, surgical treatment or complications require inpatient care. A better choice for an operational definition of disease onset would be the date of first …