Aspirin in the Prevention of Cancer

Introduction
Could aspirin, or at least the salicylate compound that is the chemical basis of aspirin, be in truth an essential substance for animals – in fact akin to the vitamins – without which we are all prone to diseases such as cancer, Alzheimer’s and heart disease?

This is not a fanciful question posed by cranks. It was seriously debated on 10th November by highly experienced scientists and clinicians at the top of their fields of research in Britain. Their meeting concentrated on the effects of aspirin in preventing and treating cancers of several organs, including the bowel, cervix, breast and skin. But it opened out into a discussion into how aspirin might produce its beneficial effects – and the implications are astonishing.

The proposal, made tongue in cheek, that salicylates might be called ‘vitamin S’ was made by Gareth Morgan, of the Public Health Service in Wales. He has been studying the association between aspirin use and cancer. He admitted that the link is not straightforward. Patients who take aspirin may be different and more health conscious than those who don’t, and early symptoms of cancer may induce people to take aspirin. However, the figures are extremely positive for aspirin use as a preventive against several forms of cancer.

He summarised the knowledge so far, using the technique of meta-analysis of many studies. They showed, from studies of nearly 3,000 cases, that there was a substantial lowering of risk of ovarian cancer in regular aspirin users. For oesophageal cancer, the ninth commonest cancer in Britain, there are data on 2000 cases. aspirin lowered the risk by half, a similar reduction to that for stomach cancer. Two studies of stomach cancer reported that the risk reduction was even greater in people whose stomachs are affected by the ulcer-inducing germ helicobacter pylori. Even in lung cancer, four of the five studies suggest there is a small benefit if smokers take aspirin. aspirin use is also associated with a 50% reduction in melanoma and leukaemia, but it may be linked to an increased risk of the lymph system disorder, non-Hodgkins lymphoma.

How could aspirin have all these beneficial effects? Gareth Morgan’s proposal stems from an understanding of what salicylate does in the plant world. All plants, including vegetables and fruits, make salicylate in times of crisis – such as when they are wounded by grazing animals or are infected by plant-disease causing viruses and fungi. Salicylate is part of the plant’s healing process, healing wounds and killing infecting organisms. It is a mainstay of the plant’s defences against disease. Could it be the same in humans? We do not make salicylate ourselves, but one reason we need to eat plants is to obtain the salicylate we need from them. Even carnivores such as big cats eat the small intestines of their prey first after a kill. This, it was proposed, may well be to ensure a plentiful supply of salicylate in their diet. Domestic cats and dogs eat grass from time to time, probably for the same reason.

He suggested that modern people are salicylate-deficient due to lifestyle factors. They eat less fruit and vegetables than previous generations, and the fruit and vegetables they do eat contain lower salicylate levels than before. This is also partly because shops do not sell bruised or damaged vegetables or fruit. Naturally salicylate levels are higher in such vegetables because the plant produces it in response to the damage. People were not so choosy in the past! Nor are they likely to go back to their old eating habits. aspirin, acetyl salicylate, might well be a good substitute.

Gareth Morgan therefore would like to see a national health policy on aspirin. It reduces the risk of cardiovascular disease and is relatively safe in low doses. Should we recommend aspirin on the basis of age alone? If everyone took it from the age of, say, 50 onwards would this be more beneficial than harmful? He calculated that aspirin, if taken from age 50, could cost £100 per Quality Adjusted Life Year. This contrasts with primary care smoking cessation programmes at £250 per QALY.

During the conference, there was much discussion and debate, and repeatedly the question of ‘so what do we do?’ was raised. Should everyone start taking daily aspirin at over 50 or 55, or 60 years old? The conference did not seek to provide an answer. Mr Morgan believes that a wide debate should be initiated as a matter of urgency. In some ways, the debate has already been started by the proposal of a polypill that contains aspirin.

There were also repeated calls for further randomised trials to be conducted to test the Aspirin and Cancer hypothesis. Yet the calls raise further interesting questions. Who will fund expensive trials on aspirin? Who will do the trials? There are no obvious candidates for the former, which makes the latter question somewhat irrelevant.

He stressed that as The Aspirin Agenda is now taken forward, two principles of wider aspirin use must be adopted. Firstly, in all situations aspirin must be considered as a complement, and not a competitor, to other interventions that promote health. Secondly, aspirin must only be used in situations within which there is good evidence that benefits exceeds risks.

He suggested that aspirin may confer on the general public a broad risk reduction against several forms of disease. It could be of substantial benefit to disease reduction programmes. Of course, more research is needed to understand better its mechanism of action and to form policies on its use.

The meeting, which was chaired by Professor Gordon McVie, Director, Cancer Intelligence, and Past Director General, Cancer Research UK, and opened by Professor Nicholas Wright, Warden of St Bart’s and the London School of Medicine and Dentistry, covered the newest research on several forms of cancer. The first speaker, Professor Chris Paraskeva, is Director of the Cancer Research UK Colorectal Tumour Biology Research Group in the Department of Pathology and Microbiology at Bristol University.