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Alex S. Woodell
Most of us have taken acetylsalicylic acid at some point in our lives. This popular drug was first brought to market in 1899 by Bayer who coined the brand name Aspirin. Aspirin belongs to a class of drugs known as nonsteroidal anti-inflammatory drugs (NSAIDs) which are used to treat pain, fever, and inflammation. Although its initial popularity declined in the late 1950s with the development of acetaminophen (Tylenol) and ibuprofen (Advil), sales spiked following a series of clinical trials in the 60s and 70s that established Aspirin’s efficacy as an anti-clotting agent. By the end of the 1980s, Aspirin was widely used as a preventive drug for heart attack and stroke. In the years that followed, several case-control studies revealed that aspirin may reduce the risk for colorectal cancer (CRC) in addition to esophageal, gastric, biliary, and breast cancer. Among these, gastrointestinal cancers were shown to be the most affected by Aspirin.
In 1988, Kune et al. first reported a correlation between CRC incidence and the use of Aspirin-containing medications using data from a large population-based study. The authors conclude that “this finding . . . has potential significance in colorectal cancer chemoprevention and merits early confirmation.” Since then, their findings have been confirmed by numerous epidemiological, case-control, and clinical trial studies. Several supporting papers spiraled out of the Cancer Prevention Programme (CaPP), an international set of clinical trials funded by the European Union, which began in 1993. Investigators found a significant reduction in Lynch Syndrome, the major form of hereditary CRC, for patients that took 600 mg of Aspirin per day for two years. The Capp3 study is currently underway to determine if lower doses of Aspirin confer the same protective effect for patients with Lynch Syndrome. Peter Rothwell, a well-known clinical neurologist at the University of Oxford, reported Aspirin’s preventive cancer effect while studying its role in cardiovascular disease (CVD). He found that daily administration of 75 mg Aspirin for five years reduced the incidence and mortality due to CRC by 30 to 40% after a 20-year follow-up. Furthermore, the protective benefit increased with duration of treatment. This growing body of evidence has convinced some experts to begin advocating for Aspirin as legitimate cancer prophylactic.
The U.S. Preventive Services Task Force (USPSTF), an independent panel of experts in disease prevention and evidence-based medicine, released a report in April 2016 recommending the use of “low-dose Aspirin for the primary prevention of CVD and CRC in adults aged 50 to 59.” While Aspirin may benefit older adults as well, the USPSTF determined that regular Aspirin-users in this age group experienced fewer heart attacks, ischemic strokes, and CRC than those aged 60-69. One reason for this discrepancy concerns latency to benefit. CVD prevention benefit begins within the first 5 years of use, while CRC prevention benefit can take anywhere from 5-20 years to manifest. Based on an approximate worldwide life expectancy of 70 years, it’s unlikely that individuals older than 60 would stand to benefit much from this treatment. Gastrointestinal bleeding, one of the primary adverse effects associated with Aspirin, is also a cause for concern; particularly, for adults above the age of 70.
Aspirin appears to be quite effective at preventing CRC, but can it prevent other types of cancer as well? A review article published in September 2018 suggests that it can. This meta-analysis pooled data from 71 studies based on statistics from over 120,000 patients taking Aspirin. They found that Aspirin reduced the number of colon cancer deaths by 25%, breast cancer deaths by 20%, and prostate cancer deaths by 15%. Additionally, “there is also evidence of a substantial reduction in the incidence of metastatic spread of these cancers.” A recent bioinformatics study suggests that this benefit may extend to many other types of cancer as well including small-cell lung, non-small-cell lung, endometrial, bladder, and renal cell carcinoma. However, these correlations are preliminary and require further validation.
A precise mechanism describing Aspirin’s prophylactic cancer efficacy has not yet been determined. However, two doctors in Italy recently published a paper in the Journal of the American College of Cardiology that offers an intriguing solution to this puzzle. A key event during cancer progression involves the biosynthesis of prostaglandin E2 (PGE2), a cell signaling molecule that influences the adhesive, migratory, and invasive behavior of tumor cells. Additionally, PGE2 enhances tumor growth and metastasis by promoting platelet aggregation around circulating tumor cells. Platelets act as a barrier, shielding the underlying tumor from type I interferons and T cells, two of the main anti-cancer regulators in the human body. Aspirin inactivates the enzymes responsible for producing PGE2, rendering tumor cells vulnerable to immune system attack. In summary, it seems that Aspirin’s antiplatelet properties may drive its preventive cancer effect.
The original Welsh proverb first recorded in the 1860s went something like this: “Eat an apple on going to bed, and you’ll keep the doctor from earning his bread.” Back then, roasted apples sprinkled with caraway seeds were commonly served as a healthy dessert. Apples have since been linked to numerous health benefits including lowering bad cholesterol levels, stroke prevention, and improving neurological health. Likewise, the list of benefits for Aspirin has grown steadily since it was first formulated in the late 1800s. Originally developed as a less-irritating substitute to common salicylate medications, Aspirin is now commonly used as a preventive treatment for heart attack, stroke, and CRC. This “wonder drug” may indeed help keep the cardiologists and oncologists away if taken regularly.
Diarmuid, Jeffreys. Aspirin: the Remarkable Story of a Wonder Drug. Bloomsbury Publishing, 2005.
Bibbins-Domingo, Kirsten. “Aspirin Use for the Primary Prevention of Cardiovascular Disease and Colorectal Cancer: U.S. Preventive Services Task Force Recommendation Statement.” Annals of Internal Medicine, vol. 164, no. 12, 2016, p. 836., doi:10.7326/m16-0577.
Patrignani, Paola, and Carlo Patrono. “Aspirin and Cancer.” Journal of the American College of Cardiology, vol. 68, no. 9, 2016, pp. 967–976., doi:10.1016/j.jacc.2016.05.083.
“File:BayerHeroin1911.Png.” Wikimedia Commons, Wikimedia Foundation, Inc., 7 Nov. 2016, commons.wikimedia.org/wiki/File:BayerHeroin1911.png.
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