By Rich Haridy April 16, 2020

A new study is presenting the most current meta-analysis of published observational research investigating whether long-term aspirin use reduces the risk of developing digestive tract cancers. While the results suggest aspirin may help prevent some cancers, some experts question how useful this kind of associational study is, particularly when a recent randomized clinical trial came to a very different conclusion.

Aspirin’s use as a preventative medicine arose in the late 20th century. First thought to reduce risk of heart attack and stroke, more recently it has been floated as a possible cancer prevention compound. However, evidence of the benefits from daily aspirin use is inconsistent, and scientists are still debating whether the risks outweigh the benefits.

A new study, led by a team of Italian researchers, is offering the largest meta-analysis conducted to date, focusing on a very specific relationship between long-term aspirin use and a reduction in incidences of digestive tract cancers. The analysis pooled data from 113 observational studies covering cancers such as bowel, pancreatic and liver.

The study defined regular use of aspirin as at least one or two tablets per week, and concluded there is a dose-dependent link between aspirin use and a reduced risk of several cancers. In general, aspirin use was associated with a 27 percent reduction in risk of colorectal cancer, a 36 percent reduction for stomach cancer, and a 22 percent reduction for pancreatic cancer. Higher doses, taken for longer periods of time, were associated with greater reductions in cancer risk according to the study.

“We found that the risk of cancer was reduced with increased dose; an aspirin dose between 75 and 100mg a day was associated with a 10% reduction in a person’s risk of developing cancer compared to people not taking aspirin; a dose of 325mg a day was associated with a 35% reduction, and a dose of 500mg a day was associated with a 50% reduction in risk,” says Cristina Bosetti, corresponding author on the new study. “However, the estimate for high dose aspirin was based on just a few studies and should be interpreted cautiously.”

The analysis suggests long-term use of aspirin confers the most benefit in reducing cancer risk, particularly in relation to colorectal cancer. The biggest benefits were seen when aspirin was used for between five and ten years, however, the researchers note few studies examine very long term (over ten years) aspirin use.

“Compared to people who did not take aspirin regularly, the risk of bowel cancer declined in regular aspirin users up to ten years,” adds Bosetti. “The risk was reduced by 4% after one year, 11% after three years, 19% after five years and 29% after ten years.”

All these results may sound like great news, and offer a green light for daily aspirin use, but it is important to note there is plenty of other research to suggest regular aspirin use is not particularly beneficial if you are otherwise healthy.

Another large meta-analysis of observational research published early last year looked at the relationship between daily aspirin use and cardiovascular events, but this analysis compared the potential benefits of aspirin against the known harms.
Pooling data from 13 studies, that analysis concluded there was a very small association between reduced cardiovascular events and aspirin use, but, aspirin use also raised the incidence of major bleeding events. The general conclusion of that analysis was daily aspirin use may do more harm than good, especially if a person is otherwise healthy and not at a high risk of cardiovascular disease.

The majority of these studies rely on observational research, homing in on correlations between regular aspirin use and incidences of disease. The gold standard for identifying causal relationships comes from randomized clinical trials, and one of the biggest conducted on the subject to date revealed interesting primary results in 2018.

Called the ASPREE trial (ASPirin in Reducing Events in the Elderly), over 19,000 subjects over the age of 70 were followed for an average of five years. At the beginning of the trial each otherwise healthy subject was randomly allocated to either a placebo group or a low-dose (100mg) aspirin group.

Despite a volume of observational study linking aspirin use to lower rates of cancer, the ASPREE trial unexpectedly found no such correlation. Little difference was seen between the placebo and aspirin groups, on almost every metric. In fact, the aspirin group surprisingly displayed slightly higher rates of all-cause mortality and cancer-related death. Even more anomalously, the aspirin group in the ASPREE trial reported more colorectal cancer deaths than the placebo group.

Andrew Chan, a professor of medicine from the Harvard Medical School, says the discordant results found in the ASPREE clinical trial compared to this new meta-analysis may indicate aspirin only reduces risk of developing cancer if started at a younger age.

“These results do differ from those of the ASPREE trial, which did not find an association with lower risk of cancer and suggested even a possible increase in death from cancer,” says Chan in an email to New Atlas. “This may be due to the fact that ASPREE only examined the initiation of aspirin in an older population. A differential effect of aspirin when started later in life requires further investigation.”

Ultimately, Chan suggests low-dose aspirin may be a reasonable cancer risk-reduction option if started between the ages of 50 and 60. He does note, however, this action should only be taken after discussions with a doctor over the risks and benefits.

Mark Nelson, from the University of Tasmania, worked on the ASPREE project and says data from his team’s clinical trial work is much more reliable than observational studies, even when those observational studies are pooled in a meta-analysis.

“This is a meta-analysis of observational study and therefore subject to residual confounding,” says Nelson, commenting on the new research. “Large prospective clinical trials with adjudicated cancer outcomes such as ASPREE are more rigorous and therefore reliable for providing evidence of harm or benefit.”

Nelson offers a clear and concise answer when asked if there is any context for otherwise healthy people to take aspirin as a preventative agent.

“No,” he says.

Carlo La Vecchia, senior author on the new meta-analysis from the University of Milan, suggests that although this research does seem to point to a beneficial effect from aspirin in the prevention of some cancers, there are many factors that need to be considered before a person starts taking the drug. Every individual has their own subjective set of risk factors, meaning there can be no broad general recommendation that applies for everyone.

“Taking aspirin for the prevention of bowel cancer, or any other cancers, should only be done in consultation with a doctor, who can take account of the person’s individual risk,” says La Vecchia. “This includes factors such as sex, age, a family history of a first-degree relative with the disease, and other risk factors. People who are at high risk of the disease are most likely to gain the greatest benefits from aspirin.”

The new study was published in the journal Annals of Oncology.

Source: European Society for Medical Oncology