Which Cancers May Be Less Likely with Regular Aspirin Use?

Regular aspirin use has once again been associated with a significantly lower cancer risk throughout the gastrointestinal tract, including pancreatic and liver cancer.

The findings were published online on April 16 in Annals of Oncology. These results come from the largest meta-analysis to date, including 113 observational studies.

Note: Meta-analyses are the most comprehensive investigations, combining the results of multiple independent studies on a particular topic and statistically analyzing the findings. Meta-analysis results constitute the strongest scientific evidence.

The current meta-analysis provides further evidence of aspirin’s beneficial effects on colorectal (large bowel) and other digestive system cancers. It also shows that longer aspirin use tends to reduce colorectal cancer risk further.

These findings, which are new for pancreatic and some other digestive system cancers, may have implications for preventing cancers with high mortality rates.

The results showed that regular aspirin use reduced digestive system cancer risk by 22% to 38% compared with nonuse.

Regular aspirin use reduces the risk of the following cancers:

• Colorectal (colon and rectal = large bowel) cancer by 27% across 45 studies.
• Esophageal cancer by 33% across 13 studies.
• Stomach cancer by 36% across 14 studies.
• Liver and biliary tract cancer by 38% across 5 studies.
• Pancreatic cancer by 22% across 15 studies.

By contrast, regular aspirin use was found to have no protective effect against head and neck cancer.

The History of Aspirin

On August 10, 1897, chemist Dr. Felix Hoffmann succeeded in producing pure acetylsalicylic acid by synthesizing salicylic acid with acetic acid. Acetylsalicylic acid, obtained from willow bark and commercially known as aspirin, has become an indispensable medicine in every home because of its practical benefits and low risk of adverse effects. Aspirin is commonly used to reduce fever, relieve pain and decrease inflammation. In addition, through its blood-thinning effect, long-term low-dose aspirin use in arrhythmias, heart failure, diabetes and vascular occlusion prevents or reduces related heart attacks, strokes and vascular problems.

Aspirin works by inhibiting enzymes called cyclooxygenases (COX). COX1 enzymes are involved in the synthesis of thromboxane A2, which contributes to blood clotting, while COX2 enzymes synthesize prostaglandins involved in sensing fever, pain and inflammation. Aspirin therefore thins the blood by inhibiting COX1 and reduces the perception of pain, fever and inflammation by inhibiting COX2. In other words, it does not treat the cause of pain or fever; it only reduces how they are felt.

The mechanism through which aspirin helps prevent cancer is still under investigation and has not been clearly established. Researchers are considering both COX-related and other mechanisms. Studies have shown that aspirin inhibits the release of a molecule called sphingosine-1-phosphate. This molecule promotes tumor growth, formation of new blood vessels feeding the tumor (angiogenesis), and inflammatory events. Preventing its release is therefore a plausible mechanism for aspirin’s cancer-preventive effect. Other signaling molecules affected by aspirin are also being investigated.

Could Aspirin Use Prevent Many Cancer Deaths?

According to the study authors, these findings suggest that regular aspirin use could prevent many deaths from gastrointestinal cancers. One striking finding was that longer aspirin use reduced cancer risk further.

For example, 1 year of aspirin use reduced colorectal cancer risk by only 4%, while 3 years of use reduced it by 11%. The daily dose was also associated with the reduction in risk.

The relative risk reduction for colorectal cancer was reported as 10% for 75 mg daily, 11% for 81 mg daily, 13% for 100 mg daily, 35% for 325 mg daily and 50% for 500 mg daily.

However, the researchers note that the estimated 50% risk reduction with the highest aspirin dose was based on only a few studies and should be interpreted cautiously. It is also unclear when aspirin should be started, and at what dose, to reduce the risk of other cancers. For example, if precancerous lesions or substantial scarring are already present in the liver, it may be too late for aspirin to provide any protective benefit against eventual liver cancer.

It is therefore difficult to recommend aspirin for preventing cancers other than colon and rectal cancer.

The United States Preventive Services Task Force says there is sufficient evidence that aspirin reduces colorectal cancer incidence in high-risk patients after 5-10 years of use.

Warning: Individuals should discuss the potential benefits and risks of aspirin use against cancer with their doctors. For someone prone to bleeding, for example, aspirin can pose a serious risk. This decision should therefore be made jointly under medical supervision.

This meta-analysis highlights the need for randomized clinical trials to establish more clearly the effect of aspirin use on reducing cancer risk.

There was strong evidence that aspirin could reduce colorectal cancer risk in particular. In 2016, JAMA Oncology published two large prospective cohort studies (the Nurses’ Health Study [1980-2010] and the Health Professionals Follow-up Study [1986-2012]), providing evidence of substantial risk reductions with long-term aspirin use (≥ 6 years): 19% for colorectal cancer and 15% for any gastrointestinal cancer.

This new meta-analysis adds information on pancreatic and liver cancers.

The authors observed a 20% reduction in pancreatic cancer, which is important given the limited options for preventing a difficult cancer such as pancreatic cancer.

They also found some evidence for reducing liver and biliary tract cancer risk, but data on the duration of aspirin use were too limited for reliable duration-risk assessments. These findings suggesting a potential benefit are important given the recent association between aspirin use and lower hepatocellular (liver) cancer risk in patients with chronic hepatitis B.

What Do Risk Reduction and Prevention Mean in Cancer?

Engaging in a risk-reducing behavior (such as taking aspirin, losing weight or stopping smoking or drinking alcohol) does not mean that the cancer will necessarily be prevented. It means that "some" people who would otherwise have developed it will not. For a numerical example, saying "aspirin use reduces colon cancer risk by 22%" means that cancer is prevented in 22 of every 100 people who would otherwise have developed it. As this shows, aspirin does not eliminate cancer risk: you can still develop colon cancer while taking it, but your risk is lower. The risk reduction is also unclear for cancers outside the gastrointestinal system. 

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