Regular Aspirin Use and Reduced Risk of Pancreatic, Liver Cancer

Regular use of aspirin has once again been linked to a reduced risk of cancer, this time showing a significantly reduced risk of cancer at all sites within the gastrointestinal (GI) tract, including pancreatic and liver cancer, which are too often fatal.

The findings come from the largest meta-analysis so far of 113 observational studies, published online April 16 in the Annals of Oncology.

"The present meta-analysis provides further evidence and quantification of a favorable effect of aspirin on colorectal and other digestive tract neoplasms [and] it also suggests that the protection tends to increase with longer duration of use, and for colorectal, with increasing dose," conclude the authors, led by Cristina Bosetti, PhD, Department of Oncology, Mario Negri Institute for Pharmacological Research, Milan, Italy.

The new findings "for pancreatic and other digestive tract cancers may have implications for the prevention of these highly lethal diseases," commented coauthor Carlo La Vecchia, MD, professor of epidemiology, University of Milan, Italy.

Results showed regular aspirin use reduced the risk of cancers of the digestive tract by 22% to 38% compared with nonuse. Regular aspirin use reduced the risk of:

Colorectal cancer (CRC) by 27% in 45 studies.
Esophageal cancer by 33% in 13 studies.
Stomach cancer by 36% in 14 studies.
Hepatobiliary cancer by 38% in five studies.
Pancreatic cancer by 22% in 15 studies.

In contrast, regular aspirin use had no protective effect in head and neck cancer.

Many Cancer Deaths Could Be Avoided

These findings suggest that many GI cancer deaths could be avoided by regular use of aspirin, La Vecchia commented in a journal press release.

Approximately 175,000 deaths from CRC are predicted to occur in the European Union in 2020, about 100,000 of which will occur in patients 50-74 years of age, he pointed out.

If regular use of aspirin doubled in this age group (increasing from 25% to 50% of these individuals), this could mean that between 5000 to 7000 deaths from bowel cancer and 12,000 to 18,000 new cases could be avoided, La Vecchia noted.

In addition, the doubling of regular aspiring use in individuals aged 50-74 years could prevent 3000 deaths from each of esophageal, stomach, and pancreatic cancer, and 2000 deaths from liver cancer.

Longer Duration, Greater Reduction of Risk

The meta-analysis found that the longer the aspirin use, the greater the relative risk reduction.

For example, with 1 year of use, aspirin reduced the risk of CRC by only 4%, and 3 years of use reduced CRC risk by 11%.

However, with 5 years of use, aspirin reduced CRC risk by 19%, and after 10 years of use, aspirin reduced that risk by 29%, researchers point out.

In addition, some of the results in CRC (based on 11 studies) suggest the higher the dose, the greater the risk reduction.

The relative risk reduction for CRC was 10% for aspirin taken at 75 mg/day, 11% for 81 mg/day, 13% for 100 mg/day, 35% for 325 mg/day, and 50% for 500 mg/day.

However, investigators point out that the 50% risk reduction estimate for the highest dose of aspirin was based on only a few studies and suggest this finding should be interpreted with caution.

New Results Go Beyond CRC Prevention

Asked for comment by Medscape Medical News, Tracey Simon, MD, MPH, of Massachusetts General Hospital and Harvard Medical School in Boston, felt the new meta-analysis adds to the existing literature by showing aspirin has a protective effect in cancers that extend well beyond CRC prevention.

"It's one of the first studies to do so comprehensively at multiple sites of gastrointestinal and hepatobiliary cancers," Simon noted. "So it's comprehensive, it's confirmatory, and it does show some associations with the more novel [digestive tract] cancers than just CRC prevention," she added.

What remains to be confirmed, however, is what dose of aspirin is optimal, especially for the more novel cancers beyond CRC, to best balance risk versus benefit.

"On top of that, we need to know what the right duration of aspirin use might be," Simon observed.

The other outstanding question for many of these other cancers is the optimal time of treatment initiation.

As Simon noted, many of these GI cancers have precursor lesions well before they progress to frank cancer, citing the example of liver fibrosis.

"We need to know at what stage of disease severity aspirin might potentially provide the most protective effect while minimizing risk," she pointed out.

Alternatively, if considerable scarring has already occurred in the liver, it is possible that it may be too late for aspirin to provide any protective benefit against eventual cancer, Simon suggested.

For these reasons, Simon and others do not currently recommend the use of aspirin for the prevention of extracolonic cancers but rather follow current guidelines.

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

"We also ask patients to talk to their doctors about what the potential risks of aspirin use are versus the benefits for them personally but there is no blanket recommendation for aspirin use in these other cancers," Simon emphasized.

Strong Support for Cancer Risk Reduction

"This well-designed, comprehensive meta-analysis strongly supports the risk reduction association between regular aspirin use and gastrointestinal cancers," said Victoria Seewaldt, MD, from the City of Hope Comprehensive Cancer Center in Duarte, California, who was asked for comment.

There is now a need for randomized, mechanistic prevention trials, she said.

There was already strong evidence suggesting that aspirin may reduce cancer risk, particularly for colorectal cancer, she noted. Two large prospective cohort studies, the Nurses' Health Study (1980-2010) and Health Professionals Follow-up Study (1986-2012), provided evidence of a strong association between long-term aspirin use (≥ 6 years) and a 19% decreased risk of colorectal cancer as well as a 15% decreased risk of any type of gastrointestinal cancer (JAMA Oncol. 2016;2:762-769).

The new meta-analysis adds information on pancreatic and liver cancers, Sweewaldt comments.

The authors observed a 20% reduction in pancreatic cancer, which is important given that there are limited options for pancreatic cancer prevention, she suggests.

They also found some evidence for risk reduction of cancers of the hepatobiliary tract, but the data for duration of aspirin use was too limited to provide accurate duration-risk assessments, Seewaldt noted. These data suggesting a potential benefit is important given the recent report that aspirin use was associated with a reduced risk of hepatocellular cancer in patients with chronic hepatitis B.

Editor's note: This article has been updated with additional comments.

The study was supported by a grant from Bayer AG. The authors and Simon have reported no relevant financial relationships.

Ann Onc. Published online April 16, 2020. Full text

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