Long-term aspirin use may reduce the risk of colorectal cancer

By Will Boggs MD

NEW YORK (Reuters Health) - Long-term, consistent use of low-dose aspirin is associated with a 27% reduction in the risk of colorectal cancer, researchers from Denmark report.

"Our results indicate that unless low-dose aspirin is taken continuously, there is little protection against colorectal cancer," Dr. Soren Friis, from the Danish Cancer Society Research Center, Copenhagen, told Reuters Health by email. "Our findings for nonaspirin NSAIDs indicate a substantial protective effect against colorectal cancer from consistent long-term use of these agents, and there was some indication that even non-continuous use of these agents may be effective for the prevention of colorectal cancer."

Most earlier studies have suggested that long-term, regular aspirin use is associated with a substantial reduction in colorectal cancer risk, and numerous studies have shown a protective effect of nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) on the development of colorectal neoplasia.

Dr. Friis's team used data from several Danish registries to investigate the relationship between the use of aspirin or nonaspirin NSAIDs and colorectal cancer risk.

Researchers found no association between ever use of low-dose aspirin and colorectal cancer risk, and only a marginally reduced risk of colorectal cancer in association with ever use of nonaspirin NSAIDs, according to the August 24 Annals of Internal Medicine online report.

Continuous use of low-dose aspirin for five years or longer, however, was associated with a 27% reduction in colorectal cancer risk.

Intensive use of nonaspirin NSAIDs (the equivalent of 0.3 standard doses daily) for five or more years was associated with a 30% reduction in colorectal cancer risk, and the use of at least two prescriptions per year for five years or longer was associated with a 36% reduced risk.

The lowest risk for colorectal cancer was seen for nonaspirin NSAIDs with the highest cyclooxygenase (COX)-2 selectivity.

Aspirin seemed to be more protective in women and among participants without a history of cardiovascular or cerebrovascular disease, whereas the protection associated with nonaspirin NSAID use did not differ according to age, sex, clinical stage, or history of cardiovascular or cerebrovascular disease.

"Our results for continuous users of low-dose aspirin should be interpreted cautiously, since these patients comprised only a small proportion of the low-dose aspirin users and might have a risk profile different from that of the general population," Dr. Friis said. "In other words, these high-compliers might have a lower risk of colorectal cancer than people in the general population due to factors we were not able to adjust for (e.g., weight, dietary factors, and physical activity) or for which our adjustment was incomplete (e.g., colonoscopy screening in the private health care sector)."

"Additional research is needed to determine the optimal dose and duration of aspirin use for colorectal cancer prevention, with due consideration of other beneficial (cardiovascular) effects and potential harms (gastrointestinal, cerebral)," Dr. Friis concluded. "The cancer preventive potential of nonaspirin NSAIDs should be explored further, if naproxen or other nonaspirin NSAIDs prove not to be associated with cardiovascular adverse events."

Dr. Gurpreet Singh Ranger, from Upper River Valley Hospital, Waterville, New Brunswick, and Dalhousie Medical School, Halifax, Nova Scotia, Canada, who recently published a review of colorectal cancer prevention with COX inhibitors (http://bit.ly/1h95Cob), told Reuters Health by email, "Low dose aspirin, already taken regularly by millions, reduces the risk of colorectal cancer. These drugs do have side effects however; for example, if taken long term, they can cause gastrointestinal bleeding, peptic ulceration, and increased risk of hemorrhage."

Dr. Ranger's advice: "Low-dose aspirin for chemoprevention -- yes; other NSAIDs and COX-2 inhibitors -- probably no, as they have a higher rate of side effects."

Dr. Michihiro Mutoh, from National Cancer Center Research Institute, Tokyo, Japan, told Reuters Health by email, "Aspirin is also useful for the colorectal tumor recurrence in the Asian population. It is surprising that aspirin use in the patients who smoke increase about three-fold the risk of recurrence, but reduced the risk in the patients who do not smoke."

"There are several candidates for cancer preventive agents, but at present, aspirin might be the best," Dr. Mutoh concluded. "We should search for other useful chemopreventive agents by the aspect of drug repositioning, e.g., statins and metformin."

The Danish Cancer Society and the Aarhus University Research Foundation supported this research. The authors reported no disclosures relevant to this paper

SOURCE: http://bit.ly/1U2XIPa

Ann Intern Med 2015.

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