1. From a case-control study, using nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin continuously for over 5 years was associated with lower risk of colorectal cancer.
2. Rectal cancer, compared to that found in the proximal or distal colon, was associated with the greatest reduction in risk after long-term, high-intensity NSAID use.
Evidence Rating Level: 3 (Average)
Study Rundown: Multiple epidemiologic studies have supported the association between long-term aspirin use and reduced colorectal cancer risk, though it is unclear whether this benefit pertains to all nonsteroidal anti-inflammatory drugs (NSAIDs). This case-control study used the drug use registry in Denmark to determine whether aspirin and other NSAID use was linked to lowering risk of colorectal cancer (CRC). Continuous long-term (≥5 years) low-dose aspirin or NSAID use, having greater than 2 NSAID prescriptions filled prior to CRC diagnosis, or any duration use of >0.1 g daily dose of a NSAID was associated with reduced CRC risk. Rectal cancer, compared to that found in the proximal or distal colon, was associated with the greatest reduction in risk after long-term, high-intensity (>0.3 g daily dose) NSAID use. When broken down by anatomic location, aspirin use of any dosage or duration was not associated with statistically significant CRC risk. Interestingly, COX-2 selective NSAIDs, compared to nonselective NANSAIDs, were associated with a slightly greater CRC risk reduction. Limitations of this study relate to the study design, as only association, but not causality, can be inferred from these results. Overall, this study adds more evidence supporting the role of long-term aspirin and other NSAIDs in decreasing CRC risk.
In-Depth [case-control study]: This study compared 10,280 known cases of CRC to 102,800 matched control participants without CRC. Cases and controls were demographically similar in every characteristic, except cases were more likely to not have had a colonoscopy (4.5% v. 7.5%). Aspirin was only linked to reduced risk of CRC if used continuously for ≥5 years (OR 0.73, 95%CI 0.54-0.99). However, non-aspirin NSAIDs were associated with reduced CRC risk if they were ever used prior to diagnosis (OR 0.94, 95%CI 0.90-0.98), used at a daily dose between 0.1-0.3 g (OR 0.89, 95%CI 0.81-0.98), used at a daily dose >0.3 g (OR 0.70, 95%CI 0.62-0.78), used for 5 to 10 years (OR 0.89, 95%CI 0.83-0.94), used for >10 years (OR 0.90, 95%CI 0.83-0.98) or used continuously for ≥5 years (OR 0.64, 95%CI 0.52-0.80). When analyzed based on anatomic regions, ≥5 years of high-dose non-aspirin NSAID use was associated with a 38% reduced risk of CRC in the rectum, 31% in the distal colon and 20% in the proximal colon.
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