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This nationwide registry-based cohort study (2004–2018) assessed the association between low-dose aspirin use and risk of colorectal cancer (CRC) in Norway. Adults (aged ≥50 years) on low-dose aspirin for the primary prevention of cardiovascular events (N = 2,186,390) were included and followed for a median duration of 10.9 years. Overall, current aspirin use was associated with a lower risk of CRC, particularly advanced forms of CRC. Increasing aspirin dose and duration of use were significantly associated with reduced CRC risk compared with never use of aspirin.
In adults aged 50 years and older on low-dose aspirin for the primary prevention of cardiovascular events, low-dose aspirin use was associated with a lower risk of CRC; risk reduction appears to be dependent on dose and duration of use.
Low-dose aspirin use and colorectal cancer risk
There have been many studies looking at aspirin use and the risk of colorectal cancer (CRC); some results have been positive and others have been negative. This study used national data from Norway including 2,186,390 individuals, of whom 579,196 were on low-dose aspirin based on the prescription database. A total of 38,577 patients were diagnosed with CRC during the average follow-up of 10.9 years.
The authors estimated the risk of CRC among individuals who took aspirin compared with the risk among those who never used aspirin, and they determined a 13% reduction in CRC risk among those who had taken aspirin (HR, 0.87; 95% CI, 0.84–0.90). They found an association between advanced disease and a greater degree of benefit. For example, there was an estimated 21% reduction (HR, 0.79; 95% CI, 0.74–0.84) in risk of metastatic CRC among individuals taking aspirin compared with those not on aspirin. The risk reduction was estimated to be 11% (HR, 0.89; 95% CI, 0.85–0.92) among patients with regionally advanced disease. Te reduction was estimated as only 7% (HR, 0.93; 95% CI, 0.87–1.00) in patients with localized disease.
The authors observed that the longer the duration of aspirin use, the better. For people with less than 3 years of aspirin use, CRC risk reduction was estimated at 9% (HR, 0.91; 95% CI, 0.86–0.95). The risk reduction was estimated at 15% (HR, 0.85; 95% CI, 0.80–0.91) with 3 to 5 years of aspirin use, and this was marginally higher at 16% (HR, 0.84; 95% CI, 0.80–0.88) for more than 5 years of use.
The authors suggested several explanations for this benefit observed with aspirin. The simplest one is that aspirin increases the risk of gastrointestinal bleeding; hence, patients are more likely to be investigated and polyps and other conditions can be taken care of before they get to the cancerous stage or the more advanced stages. However, not everyone who benefited from aspirin use underwent a colonoscopy so that can’t be the complete explanation.
A more sophisticated explanation is that aspirin blocks the mutated APC gene.1 The non-mutated version of this gene is tumor-suppressing. It produces a protein that controls cell adhesion and migration. A mutated APC gene would produce a protein that does not do its job; hence, cell adhesion and migration could lead to development of cancerous cells and metastasis.
Aspirin also irreversibly inhibits the COX enzyme, which is needed to produce prostaglandin E2, which drives proliferation, inflammation, and angiogenesis. These are all processes that are needed for cancer formation.
Rofecoxib (Vioxx), a COX-2 inhibitor was associated with a reduction in polyp formation.2 Therefore, prostaglandin E2 reduction might be one of the mechanisms behind polyp formation, and, in the long run, CRC risk. Of course, rofecoxib was associated with increased cardiovascular events. Hence, this drug is no longer available. However, aspirin is readily available and relatively inexpensive.
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