Long-term use of low-dose aspirin reduces the number of colorectal cancer cases by a quarter and reduces the death rate by more than a third. The findings were recently published on the Lancet website ((www.thelancet.com) and are forthcoming in the new issue of The Lancet. The study was carried out by Professor Peter Rothwell and colleagues at the John Radcliffe Hospital, University of Oxford. Colorectal cancer is the second most common cancer in the developed world, with a 5% risk of developing it, and around 1 million new cases and 6 million deaths worldwide each year. Most colorectal cancers develop from adenomas or polyps, and removal of polyps through sigmoidoscopy and colonoscopy can reduce the risk of cancer development. However, the test is not completely effective, especially for sigmoidoscopy, which cannot reach the proximal colon and is often missed during the examination. The same group published in The Lancet in 2007 that long-term application of high doses of aspirin (≥500 mg/day) could reduce the incidence of colorectal cancer, but side effects such as increased bleeding limit its potential as a long-term preventive drug. In addition, the study was so small that it was not possible to see effects on tumors at different sites in the colon and rectum. This new study by Rothwell and colleagues evaluated for the first time the effect of long-term application of low-dose aspirin (75-300 mg/day) on the incidence and mortality of colorectal cancer. They followed five randomized clinical studies for up to 20 years. The authors studied four clinical trials originally designed to look at the effect of aspirin on cardiovascular disease prevention to determine the effect of aspirin on colorectal cancer. In four groups of trials taking aspirin and one group using placebo (mean duration of treatment 6 years), 14,033 patients developed colon cancer in 391 cases (2.8%) during a median follow-up period of 18.3 months. A pooled analysis of patient data showed a 24% reduction in the 20-year incidence of colon cancer and a 35% reduction in mortality among patients taking aspirin. The results were consistent with trial expectations, with no increase in benefit at doses of aspirin above 75 mg. The data also showed a reduction in the absolute 20-year risk of colorectal cancer from 3.5% to 1.5% after five years of taking 75-300 mg of aspirin daily. The authors found that the majority of the reduction in colorectal cancer incidence and mortality was due to a 70% reduction in the risk of proximal colon cancer incidence and mortality, but the risk of distal colon cancer incidence and mortality remained unchanged, and the reduction in the risk of rectal cancer incidence and mortality was minimal. sigmoidoscopy reduced colorectal cancer mortality by 43% and incidence by 1/3 among participating patients. The authors believe that this new study will upset the delicate balance of recent debates about the risks-benefits of long-term aspirin use, and instead tend to draw useful conclusions. They conclude, “The five trials we investigated were conducted before colon polyp endoscopy – which also reduces colorectal cancer incidence and mortality, and thus may somewhat reduce the absolute benefit of long-term aspirin use. However, the unique inhibitory effect on fast-growing tumors that aspirin presumably possesses could justify a reduction in screening frequency. The preventive role of aspirin for proximal colon cancer is important and could compensate for the deficiencies of sigmoidoscopy. So the combination of the two approaches for the prevention of colorectal cancer would be very beneficial.” He also mentioned that following the publication of Atkin and colleagues’ findings, the UK government announced a nationwide sigmoidoscopy programme at the recent Conservative Party conference, adding, “This new finding on the efficacy of low-dose aspirin should be added to the public sigmoidoscopy programme as an additional as an additional means of preventing colorectal cancer. In a related commentary, Dr. Robert Benamouzig and Dr. Bernard Uzzan of Avicenne Hospital in Bobigny, France, said: “This interesting finding may lead clinicians to use aspirin for primary prevention of colorectal cancer, especially in those at high risk. Specific guidelines for aspirin chemoprevention should be the next step in research.