The Lancet: Important Advances in Aspirin’s Cancer Prevention

Aspirin’s cancer-proofing skills have finally welcomed heavy clinical evidence. Yesterday, the top medical journal, The Lancet, published a key study by Professor John Burn’s team at the University of Newcastle in the UK: People at high risk of inherited mutations who were at high risk of taking aspirin for more than two years in a row could reduce the risk of bowel cancer by 50 per cent;

The Lancet: Important Advances in Aspirin's Cancer Prevention

Screenshot of the front page of the paper

When it comes to aspirin prevention against cancer, we should not think that it is only in recent years the rise of the hot research direction.

In fact, as early as 1988, scientists observed the cancer-proofing potential of aspirin in case-control studies. It’s been a mess ever since. According to incomplete statistics, more than 100 observational studies have found the anti-cancer effects of aspirin.

In recent years, this research topic has been particularly hot, with many retrospective studies finding that aspirin use is associated with a reduced incidence of cancer, and many basic studies have found molecular mechanisms for aspirin to fight cancer and prevent cancer. However, there are also many studies that have found no relationship between the two. (To learn more about past research, look back at the “Aspirin Album” at the beginning of the article)

“I had an idea 30 years ago that people with genetic predispositions to colorectal cancer could help us understand whether aspirin can actually reduce the risk of cancer. Professor John Burn said.

So Professor Burn decided to study people with Lynch syndrome. Lynch syndrome, also known as hereditary non-polypsidiopathic colorectal cancer, carries pathogenic mutations in genes such as MLH1, MSH2, MSH6, PMS2, or EPCAM that can lead to DNA mismatch repair defects.

According to current data, Lynch syndrome accounts for about 3% of all bowel cancers. Although this percentage is low, about 80 percent of people with Lynch syndrome end up with colorectal cancer. In addition to bowel cancer, Lynch syndrome has been associated with a high incidence of cancer in several areas such as endometrial cancer.

The Lancet: Important Advances in Aspirin's Cancer Prevention

Professor John Burn

After years of preparation, in 1999, with the support of Cancer Research UK and a number of organisations and institutions, including the European Union, the research team led by Professor Burn launched the CAPP2 (Cancer Prevention Programme) study.

Between January 1999 and March 2005, 1,071 people with Lynch syndrome were recruited at 43 clinical research centers worldwide, 937 of whom were eligible for admission.

Eventually, 861 patients were willing to participate in the clinical study, with an average age of 42. All patients were randomly divided into two groups, one group of 427 people who took 600 mg of aspirin a day for two or four years (the patient decides), and the other group of 434 people, who took a placebo daily.

The main endpoint of the study was the number, size and histological stage of colorectal cancer detected two years after aspirin intervention;

The Lancet: Important Advances in Aspirin's Cancer Prevention

Study flowcharts

In 2008, after all patients had completed aspirin interventions, the researchers analyzed data and found that aspirin had no preventive effect. However, previous studies have found that aspirin’s protective effects are later, so the researchers decided to extend the follow-up time.

By 2011, when the first patient to receive an aspirin intervention had followed up for 10 years and an average follow-up time of 4 years and 7 months, the researchers analyzed data again: The intentional treatment analysis showed that aspirin’s preventive effect on colorectal cancer remained less significant than that of placebos. However, when the researchers only analyzed patients who had been in the same state for more than two years, they finally observed the protective effects of aspirin.

Nine years after the second data analysis, the researchers analyzed data from the CAPP2 study again. This time, all patients followed for more than 10 years, and participants in the UK, Finland and Wales followed up for even 20 years.

Overall, 74 people in the aspirin intervention group were diagnosed with cancer with a 17 per cent incidence rate, and 89 in the placebo control group were diagnosed with a 21 per cent incidence. The difference between the two groups of intentional treatment analysis was not significant, and if only patients who took the drug for more than 2 years were analyzed, the risk of aspirin group decreased by 37%, with significant differences. The two groups were similar in adverse events and compliance.

The Lancet: Important Advances in Aspirin's Cancer Prevention

Comparison of data from different subgroups of patients in two groups

Specifically, 40 people in the aspirin intervention group were diagnosed with bowel cancer with a 9% incidence rate, and 58 people in the placebo control group were diagnosed with a 13% incidence rate. Intentional treatment analysis showed a 35 percent lower risk of bowel cancer in the aspirin intervention group compared to the placebo control group, with significant differences between the two groups. If only patients who have taken the drug for more than 2 years are analyzed, the risk is reduced by 44% and the incidence is directly halved.

In the study of the preventive effects of aspirin on other cancers alone, the researchers found no significant differences.

The Lancet: Important Advances in Aspirin's Cancer Prevention

Effect of aspirin in different tumor types, different intervention time groups

Based on the above findings, Andrew Chan and Matthew Yurgelun of Harvard Medical School summarize the following:

First, patients with Lynch syndrome can significantly reduce the risk of bowel cancer by taking 600 mg of aspirin daily;

Second, the protective effect of aspirin, after 5 years to appear, early observation is not;

Third, the protective effect of aspirin is long-lasting and can last for 20 years;

Fourth, aspirin also seems to have a preventive effect on endometrial cancer, aspirin group 7 patients, control group of 17 patients, although not statistically significant, but worthy of further study.

In fact, there have been many guidelines in recent years that suggest that people with Lynch syndrome should consider aspirin, and the findings reinforce this recommendation.

Still, the researchers believe that for the Lynch syndrome group, the optimal dose and timing of aspirin require further study. Because the CAPP2 study involved a younger group of patients, previous A SPREE studies found that the effects and side effects of aspirin in the over-65s were significantly different from those in younger people.

In any case, however, this study may suggest that age in the age of 40 may be the best time to intervene for the Lynch syndrome group.

Professor Burn said he and his team were conducting a CAPP3 study that recruited 1,882 people with Lynch syndrome to see if smaller, safer doses of aspirin had the same anti-cancer effects.

The Lancet: Important Advances in Aspirin's Cancer Prevention

Finally, although there are many recommendations in the guidelines, people with Lynch syndrome should consult a doctor before deciding to take aspirin to prevent bowel cancer to ensure safety and optimal results.

We also look forward to the success of the CAPP3 study.