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Precision Medicine: Who Benefits from Aspirin to Prevent Colorectal Cancer?

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Aspirin and DNA StethoscopeIn recent years, scientific evidence has begun to accumulate that indicates taking aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) on a daily basis may lower the risk of developing colorectal cancer. Now, a new study provides more precise information on who might benefit from this particular prevention strategy, as well as who might not.

Published in the journal JAMA, the latest work shows that, for the majority of people studied, regular use of aspirin or NSAIDs was associated with about a one-third lower risk of developing colorectal cancer. But the international research team, partly funded by NIH, also found that not all regular users of aspirin/NSAIDs reaped such benefits—about 9 percent experienced no reduction in colorectal cancer risk and 4 percent actually appeared to have an increased risk [1]. Was this just coincidence, or might there be a biological explanation?

By mining mountains of data generated by 10 “cohort” studies that followed large groups of people over long periods of time, the international research team, partly funded by NIH, took aim at a dilemma that confronts many people who take aspirin on a daily basis. While aspirin is often used to relieve pain and to lower risk of heart attack or stroke, it can cause potentially serious bleeding in the stomach, small intestine, or even the brain. So, it would be great to have more precise ways to predict whether the benefits of aspirin are likely to outweigh the risks in an individual patient.

In their meta-analysis involving more than 17,000 people—half of whom had invasive colorectal cancer and half of whom did not—the international research team, led by Andrew Chan of Massachusetts General Hospital in Boston and Ulrike Peters and Li Hsu of Fred Hutchinson Cancer Center in Seattle, identified some relatively uncommon genetic variants that appear to be associated with development of colorectal cancer despite daily use of aspirin or NSAIDs. If these findings are confirmed in follow-up studies and in other population groups (the current analysis involved only people of European descent), it may point the way to the first tests that provide precise guidance on who should consider taking aspirin or NSAIDs for colorectal cancer prevention, as well as who might want to steer clear of this preventive approach.

Besides regular use of aspirin/NSAIDs, other lifestyle changes that may reduce the risk of colon cancer include losing weight, exercising more, quitting smoking, and limiting alcohol intake. Detection and removal of pre-cancerous colorectal polyps through colonoscopy, sigmoidoscopy, or fecal occult blood screening after the age of 50 is another proven strategy for preventing colon cancer, which currently is the No. 3 cancer killer in the United States [2].

Because the studies analyzed in the JAMA paper gathered data on each participant’s DNA sequence, medication use, and health status, researchers were able to examine the combined influences of genetic factors and regular use of aspirin/NSAIDs on the risk of developing colorectal cancer. Using this approach, a large group of regular aspirin/NSAID users was identified that had a lower-than-usual risk of colon cancer, along with a much smaller subset that did not. Researchers went on to determine that about two-thirds of people in the small subset without aspirin benefit had a relatively uncommon genetic variant on chromosome 15, located in the general vicinity of genes known to be involved in inflammation. The remaining one-third—individuals whose aspirin/NSAID use was associated with a greater risk of invasive colorectal cancer—shared one or two even rarer genetic variants on chromosome 12, also located in the neighborhood of genes involved in inflammation. Intriguingly, some of these genes regulate prostaglandins, a group of inflammatory compounds proposed to play a central role in driving colorectal cancer.

It still remains to be determined exactly how these uncommon genetic variants and/or nearby sections of DNA offset the properties of aspirin that guard against colorectal cancer in most people. But researchers speculate that it may have something to do with an increased tendency towards inflammation that is for some reason resistant to aspirin’s anti-inflammatory effects.

While I’m heartened by the progress we are making towards more precise prevention strategies for colorectal cancer, much more work is needed to generate the scientific evidence needed to make similar advances for other types of cancer, as well as many other diseases and conditions. Building such a foundation is one of the goals of the new Precision Medicine Initiative, which is being led by NIH. I encourage you all to learn more about that pioneering effort and its potential to revolutionize our health.

 References:

[1] Association of aspirin and non-steroidal anti-inflammatory drug use with risk of colorectal cancer according to genetic variants. Nan H, Hutter CM, Lin Y, Peters U, Hsu L, Chan AT, et al. JAMA 2015;313(11):1133-1142.

[2] What are the key statistics about colorectal cancer? American Cancer Society, Feb. 27, 2015.

Links:

Colon and Rectal Cancer (National Cancer Institute/NIH)

Colorectal Cancer Prevention (National Cancer Institute/NIH)

Andrew Chan Research Group, Massachusetts General Hospital, Boston

Peters Studies, Fred Hutchinson Cancer Center, Seattle

Precision Medicine Initiative (NIH)

NIH Support: National Cancer Institute; National Heart, Lung, and Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases

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