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COX-2 inhibitors with a statistically significant 34% reduction in overall adenoma recurrence risk (RR 0.66, 95% CI 0.60–0.72) and a 55% reduction in advanced adenoma incidence (RR 0.45, 95% CI 0.35–0.58) in a population of individuals with a previous history of colonic adenomas. However, no data are available for COX-2 inhibitors for the general population [1] . Although these data are promising, it should be mentioned that both aspirin and COX-2 inhibitors are associated with adverse effects like dyspepsia, gastrointestinal bleeding and haemorrhagic stroke ( table 1 ). Therefore, it will still be important to consider the risk-benefit ratio before recommending these agents for general chemoprevention. Whereas chemoprevention aims to prevent the development of CRC, the use of FOBT and screening colonoscopy target at the early detection of colonic lesions like adenoma or early CRC. It was promptly assumed that early detection and removal of colonic adenomas has the potential to prevent the development of CRC. A systematic review done through the Cochrane Collaboration, examining all CRC screening randomized trials that involved FOBT on more than one occasion, showed that trial participants allocated to screening had a 16% lower CRC mortality (RR 0.84, 95% CI 0.78–0.90) [3] . Colorectal cancer (CRC) is the cause of death in more than 600,000 people worldwide and is one of the most frequent cancers in the Western world. Therefore, the search for effective strategies for prevention or detection of adenomas or early CRC with the potential of cure has a high priority. In several countries the current practised strategies include fecal occult blood testing (FOBT) and/ or screening colonoscopies for the detection of colonic cancer or removal of colonic adenomas (polyps). One of the most promising agents for chemoprevention is aspirin or a cyclooxygenase-2 (COX-2) inhibitor like celecoxib. In the general population, a significant 26% reduction in CRC incidence by aspirin intake was demonstrated in studies with a 23-year follow-up (relative risk (RR) 0.74, 95% confidence interval (CI) 0.57– 0.97) [1] . In addition, an analysis of aspirin versus no aspirin in individuals with a history of adenomas or CRC has shown a statistically significant 21% reduction in risk of adenoma recurrence (RR 0.79, 95% CI 0.68–0.92) [1] . A very recent study on the long-term effect (56 months) of aspirin on cancer risk in carriers of hereditary CRC (CAPP2 Trial) confirmed this positive effect and reported a reduced risk of CRC (incidence rate ratio 0.56, 95% CI 0.32 –0.99, p = 0.05) [2] . Similar data are available for Published online: April 21, 2012

A Further Piece of the Puzzle: Positive FOBT, Colonoscopy, Aspirin and the Prevention of Colorectal Cancer