Aspirin, obesity and inherited bowel cancer – what’s the story?

The potential for aspirin to prevent cancer is an exciting prospect, even if there are still many unknowns.

We’ve written at length about it before, but here’s a quick recap on the state of play: while it certainly seems to have benefits for some, aspirin also can have side effects, and there are several key questions to answer before it can be recommended for regular use against cancer.

For example, who should take it? How long they should take it for? When they should start and stop taking it? And what dose should they take?

But the idea of a simple pill to reduce the chances of cancer is obviously a tantalising prospect.

So it was no surprise to see the results of another aspirin cancer prevention trial hit the headlines this morning.

Unfortunately, these headlines were somewhat misleading, reporting that ‘aspirin could cancel out cancer risk’ in people who are obese. This missed out a crucial detail: this finding only applies to people who have an inherited genetic syndrome that greatly increases their cancer risk.

So what’s the science behind this morning’s headlines?

Was it true?

The first thing to note is that this latest study was conducted solely in people with a condition called Lynch syndrome. Also known as ‘hereditary non-polyposis colorectal cancer’, or HNPCC, this is an inherited condition which puts people at a high risk of developing early onset bowel cancer, as well as a number of other cancers. So, not your average Joe.

In fact, about 90 out of 100 men, and 70 out of 100 women with the condition develop bowel cancer by age 70 – this compares to about seven out of 100 men and five out of 100 women in the general population.

And most bowel cancers aren’t linked to this syndrome – it’s estimated that only about four in every 100 people who develop bowel cancer do so because they have the condition. Consequently – as we’ve said – the findings of this study don’t apply to everyone, only some people with this inherited condition.

Today’s results, published in the Journal of Clinical Oncology, were the latest in a series  from a large UK clinical trial called CAPP2, which has been running for 16 years, and was designed to test whether taking regular aspirin could lower the risk of developing cancer in people with Lynch syndrome. It’s being co-ordinated by researchers in Newcastle and Sheffield, but involves people with Lynch syndrome from 16 different countries, and is funded by several organisations, including Cancer Research UK.

Participants were given either aspirin or a placebo for two years, and then followed for up to 10 years to see if they developed cancer. Results published back in 2011 showed that aspirin could indeed reduce their risk of developing bowel cancer.

What’s new?

This finding only applies to people who have an inherited genetic syndrome that greatly increases their cancer risk

The results that hit the headlines today were a reanalysis of the data from the CAPP2 trial, focusing on those participants who were overweight and obese.

The researchers found that these people had an even greater increase in bowel cancer risk, compared to those in the trial who were a healthy weight.

But among different sub-groups of people, some of these results weren’t ‘statistically significant’ (meaning there’s uncertainty over how valid they are) – the effects appeared strongest in men and those who were obese (rather than just overweight), and were only significant in those with one of the four different genetic faults that causes Lynch syndrome.

However, when the researchers looked at the people taking aspirin, those who were overweight and obese had no greater risk than people who were a healthy weight. So it looks as though, in people with Lynch syndrome, aspirin could potentially cancel out the effect being overweight or obese. This is an important finding.

But here’s a great big caveat: that’s not the same as aspirin cancelling out the affect of being overweight or obese among people in the general population – as most of today’s headlines implied.

And even for this high-risk group of people, there are still some questions that need to be answered before doctors can start recommending they take aspirin regularly. For example, it’s not yet known if these results apply to men and women, the different types of Lynch syndrome, and all weights above the healthy range. And the actual number of bowel cancer cases among the 937 participants was relatively small: just 55.

It’s also uncertain what the most effective dose of aspirin to take is.

To answer these questions, we’re funding the CAPP3 trial, which will determine the correct dose of aspirin to take, while looking to confirm the CAPP2 trial’s findings.

Until we know more, people with a family history of bowel cancer should talk to their doctor about regular screening and the best options for them.

Unclear mechanisms

And there’s more we need to learn too. While we know that overweight and obese people may be at an increased risk of up to 10 types of cancer, and that aspirin can protect against some types of cancers, crucially, we don’t know exactly either how obesity causes cancer – nor how aspirin can protect against it.

But there are clues. For example, extra fat in the body can have harmful effects, like producing hormones and growth factors that affect the way our cells work. One idea is that obesity is linked to an inflammatory response, which leads to an increased risk of cancer. So an explanation of the trial’s findings may be that aspirin suppresses this inflammation.

But there’s a way to go yet before this is proven – and there are other theories too that need to be ruled out (for example, it could be something to do with the way insulin affects our cells, or the way obesity influences our immune system).

And it’s also possible that the way aspirin reduces bowel cancer risk in people with Lynch syndrome is different from the way it seems to do so in the rest of us. Only when we know for sure, can we be confident that the CAPP2 results can be applied more widely.

There is, however, an intriguing finding buried in this analysis, which the media missed.

Although it wasn’t statistically significant, the finding that obesity only increased cancer risk in one of the four different subtypes of Lynch syndrome – caused by faults in a gene called MLH1 – chimes in with other groups’ findings, suggesting it’s worthy of further research. And understanding why this might be the case could yield important clues as to how bowel cancer develops in the first place –  which could, in turn, inspire new ways to prevent and treat it.

Same for everyone else?

Today’s headlines make quite a big leap from the study results. They assume that, because aspirin is effective in protecting against bowel cancer in overweight and obese people with Lynch syndrome, it has the same effect in everyone who was overweight and obese.

But there’s no evidence to suggest that’s the case – there are no reliable data, yet, that show taking aspirin is effective at protecting against cancer in overweight people in the general population.  However, it will be interesting to see where this area of research leads in the future.

What we do know is that, healthy weight or otherwise, taking aspirin has the potential to protect against some types of cancer – but it can also have serious side-effects in some people, including lethal strokes and gastric bleeds, and serious peptic ulcers.

So if you’re thinking about taking aspirin regularly – for whatever reason – your GP should always be your first port of call.

– Casey Dunlop is a health information officer at Cancer Research UK