Can aspirin reduce bowel cancer risk?

“Taking two aspirin a week could protect against cancer,” reports the Daily Telegraph. The Express suggests we should take it daily.

In a study of more than 130,000 US health professionals, who were followed up every two years for around 32 years, researchers found that aspirin use twice or more per week was associated with a 3% reduction in cancer risk. However, when analysed by cancer type, there was only one significant link – for bowel cancer – with a 19% risk reduction for aspirin use.

For protection against bowel cancer, it seemed that a 0.5 to 1.5 standard dose of tablets (325mg) per week (roughly equivalent to a daily low-dose aspirin), for more than five years, was required.

There are several limitations to this research, including the potential for unmeasured health and lifestyle factors confounding the results, and inaccurate recall about aspirin use.

But, most importantly, regular aspirin use carries the risks of stomach irritation, bleeding and ulceration. For people prescribed aspirin for cardiovascular disease, the benefits are considered to outweigh these risks. However, it is a different matter for those taking aspirin for possible cancer protection.

Until this risk-benefit balance is better understood, no recommendation can be given for everyone to take daily aspirin to reduce cancer risk. 

Where did the story come from?

The study was carried out by researchers from the School of Public Health and Harvard Medical School, Boston; Brigham and Women’s Hospital; and Massachusetts General Hospital. The study was published in the peer-reviewed medical journal JAMA Oncology and was funded by the National Institutes of Health.

You can read the study for free online.

The study was, on the whole, well covered by the UK media, hailing aspirin as a cheap drug that will cut cancer risk. Most stories did reflect the researchers’ caution that people should be informed about the potential side-effects of regular aspirin treatment. They also warned that aspirin use should not be viewed as a substitute for bowel cancer screening.

What kind of research was this?

This was a study of two US cohorts that aimed to examine the effects of aspirin on the risk of cancer – both overall and by specific cancer type.

Aspirin is a well-established drug for the treatment and prevention of cardiovascular disease. Many large trials of people taking regular aspirin for cardiovascular disease have also suggested that it may reduce the overall risk of cancer as well.

There was limited data to give reliable risk information by cancer type, with the exception of a link with colorectal (bowel) cancer. As such, the US Preventive Services Task Force recently recommended the use of aspirin to prevent bowel cancer and cardiovascular disease for many US adults. However, questions remain on optimal dose and duration of use, and whether there may be effects on other cancers. This study aimed to examine this.

The main limitations with observational cohort studies are the possibility that other health and lifestyle characteristics of the individuals may be involved in any link.  

What did the research involve?

The research involved 135,965 men and women taking part in two large US cohort studies:

• The Nurses’ Health Study (NHS), which recruited 121,700 female nurses aged 30 to 55 in 1976
• The Health Professionals Follow-up Study (HPFS), which included 51,529 male health professionals aged 40 to 75 in 1986

Both studies followed participants, with questionnaires every two years assessing health and lifestyle factors, including any diseases.

Aspirin use was assessed from the start of the HPFS study in 1986, and from 1980 in the NHS study, and every two years subsequently in both studies.

The questions on aspirin use varied. For example, in HPFS from 1986, people were asked whether they took aspirin twice or more a week, then from 1992 they were asked to quantify the number of tablets per week. Both cohorts were asked about standard dose (325mg) aspirin until 2000 onwards, when they were asked to separately report low-dose or standard-dose aspirin.

Cancer outcomes were assessed up to 2014/15 using the questionnaires, and by checking with the US National Death Index. They analysed the link between aspirin use and any cancer or by specific cancer site, taking into account various potential confounders, including ethnicity, height, body mass index (BMI), smoking, diet and alcohol use.

What were the basic results?

The total follow-up period was 32 years. During this time, 20,414 cancers were found in 88,084 women, and 7,571 cancers were found among 47,881 men.

Compared with non-regular aspirin use (taking no aspirin or less than twice a week), regular use was associated with a 3% reduced risk of any cancer (relative risk [RR], 0.97, 95%; confidence interval [CI] 0.94 to 0.99).

By cancer type, a significant risk reduction from regular aspirin was only observed for colorectal cancer (RR 0.81, 95%; CI 0.75 to 0.88) or those defined as gastrointestinal (digestive) tract cancers (RR 0.85, 95%; CI 0.80 to 0.91). However, there was no significant link between aspirin and risk of cancer of the throat and stomach, pancreas, prostate, breast, lung, “other gastrointestinal tract”, or “non- gastrointestinal tract”.

The apparent benefit of aspirin for bowel cancer appeared to be dose-dependent. The risk reduction was observed from a dose of 0.5 to 1.5 standard-dose tablets per week, and decreased further with 2 to 5 or greater tablets per week. Aspirin needed to have been taken for more than five years to observe a risk reduction.

The researchers calculated that if everyone were taking regular aspirin, then this would reduce the number of overall cancer cases by 1.8%, and the number of bowel cancer cases by 10.8%.

How did the researchers interpret the results?

The researchers conclude: “Long-term aspirin use was associated with a modest but significantly reduced risk for overall cancer, especially gastrointestinal tract tumours. Regular aspirin use may prevent a substantial proportion of colorectal cancers and complement the benefits of screening.”

Conclusion

This study has made use of long-term follow-up data from two large US studies to examine the link between regular aspirin use and risk of cancer.

The research did find that regular use of aspirin was associated with a very small reduction in the overall risk of cancer. When looking by cancer type, the only cancer with a clear risk reduction from aspirin use seems to be bowel cancer. There were no significant links for any other cancer type (the definitions of a reduced risk for “gastrointestinal tract cancers” but no link for “other gastrointestinal tract cancers” seem rather unclear). 

The risk reduction for bowel cancer seems to start from taking 0.5 to 1.5 standard-dose tablets (325mg) per week, which is roughly equivalent to a daily low-dose aspirin. It seems you need to take it for more than five years to get the benefit.

Before everyone in the country reaches for the aspirin, there are several important limitations to keep in mind:

• There does seem to be a link with reduction in bowel cancer risk, but we don’t know why this is. The researchers have taken into account many health and lifestyle factors that could be associated with the link, such as smoking, alcohol and diet. However, we don’t know that the effects of these have been fully taken into account, or whether there may be other unmeasured factors influencing the link.
• Aspirin use, frequency and dose were all self-reported by questionnaire, which increases the possibility of inaccurate recall. Any links with specific aspirin dose are likely to be less reliable in an observational study such as this than they would be in a trial – for example, where people are given a specific dose to take and investigators have better knowledge of what people are actually taking.
• This is a large sample size, but they are all US health professionals who may have specific characteristics, meaning that the results can’t be applied to all populations. 
• Probably most importantly – aspirin isn’t without side effects. Regular use can cause stomach irritation, bleeding and ulceration, with groups such as the elderly being at higher risk of these side effects. For those prescribed aspirin for cardiovascular disease, the benefits in terms of reducing risk of heart and vascular disease events are considered to outweigh the risks of the medication. However, when it comes to everyone in the population taking aspirin for possible cancer protection, this is a completely different matter.

Overall, the link between aspirin and cancer risk – bowel cancer, in particular – definitely needs further consideration. But it needs to be clarified exactly which dose and frequency would give the best balance of effectiveness against safety, and for which population groups the benefits would outweigh the risks.

Until this risk-benefit balance is better understood, no recommendation can be given for everyone to start taking daily aspirin to reduce cancer risk. 

Links To The Headlines

Daily aspirin slashes the risk of cancer: Even quarter of a tablet reduces the risk of bowel disease by 20%. Daily Mail, March 4 2016 

Taking two aspirin a week could protect against cancer. The Daily Telegraph, March 3 2016

Daily dose of aspirin ‘could SLASH risk of bowel cancer by a FIFTH’. The Express, March 3 2016

Links To Science

Yin Cao, Reiko Nishihara, Kana Wu, et al. Population-wide impact of long-term use of aspirin and the risk for cancer. JAMA Oncology. Published online March 3 2016