HOW TO PREVENT CANCERS

The documented benefits of aspirin go back, literally, thousands of year.  As early as the fifth century B.C., Hippocrates noted that a bitter willow bark extract - which contained chemicals very similar to today's aspirin - was effective at relieving pain.  Since then, aspirin has become the most commonly used medicine in the world, and its benefits have been shown to reach well beyond pain relief to include the prevention of heart attack, stroke, and now cancer.

Studies have shown for a number of years that taking a daily aspirin could lower the risk of developing and dying of colon cancer, with the latest large analysis by Rothwell and colleagues finding a 25 percent drop in the risk of developing the disease, and a 35 percent risk of dying from it, with as little as 75mg of aspirin a day (previous post; study).

Now, a new analysis by Rothwell and colleagues - which combined data on over 25,000 participants in eight randomized controlled trials - shows big reductions in the risk of cancer deaths with aspirin use, not only for colon cancer, but for a broad range of individual cancers, and for cancer overall (study).   Daily aspirin use for five or more years lowered the risk of cancer death overall by 34 percent compared to placebo.

Strikingly, the benefits persisted, and even expanded, long after the end of the trials and the aspirin treatment.  After up to 20 years of follow-up, overall cancer deaths were 22 percent lower in the aspirin group compared to placebo.  The risk of esophageal cancer death was 58 percent lower.  The risk of colorectal cancer death was 40 percent lower, and lung cancer deaths nearly 30 percent lower.

In general, the longer the daily aspirin use, the more robust the cancer benefits.

The findings of this latest study, combined with all the previous ones, could possibly rebalance the discussion of the risks and benefits of aspirin use.  When looking at aspirin's benefits in the past, the focus was largely on the heart benefits, and while these benefits could be substantial, they still needed to be balanced with the risks that go along with aspirin use, most commonly an increased risk of bleeding in the GI tract and possibly the brain.

With long term demonstrated benefits in lowering cancer deaths, which persist even after daily aspirin use of 5 - 10 years, the balance may be tipping toward the benefits of aspirin outweighing the risks for a broader swath of the population than is currently recommended (which is largely limited to those at high risk of heart attack).

At the cost of just pennies a day, it may just be what the doctor ordered.

Related CNiC Posts
Aspirin
Data Snapshot

One of the key foundations of epidemiology is causation (Hill’s causal criteria were first detailed in 1965) – and that conclusions about causation are based on a number of factors including a plausible biologic mechanism. Thus, research papers outlining associations between risk factors and disease typically outline the likely or possible mechanisms that would link the risk factor with the disease endpoint. Despite convincing evidence from observational studies that link numerous risk factors with cancer endpoints, in most cases we can’t point to a mechanistic pathway and say “this is how.” In part, this is likely because many risk factors operate through multiple pathways. But understanding those pathways remains an important priority in cancer prevention research.

While a sufficient body of evidence exists that numerous independent bodies have concluded that physical activity is causally related to a reduced risk of several cancers, including colon and breast, the mechanisms remain relatively poorly understood. A few candidates are typically mentioned and are the focus of most current research in this area – physical activity has anti-inflammatory effects, reduces insulin resistance and may alter sex hormone levels.

Mechanism studies tend to be conducted in animals or cell lines and if conducted in humans, tend to be relatively small or from non-randomized trials. This week, results came from one of the largest supervised exercise training randomized controlled trial studies conducted in women. 316 women between 18 and 30 were enrolled in a 16 week aerobic exercise intervention. The women randomized to the intervention arm participated in physical activity at levels recommended by public health guidelines: at least 30 minutes of activity at least 5 times a week. Adherence and retention rates were both high indicating a methodologically rigorous study.

Overall, the study found little that could be a link in the causal pathway between activity level and cancer.  The insulin-like growth factor (IGF) family of hormones and binding proteins, which are involved in growth and development, have long been suspected as possible mediators between exercise and cancer.  Yet, apart from a statistically significant lower level of IGFBP-3 in controls, none of the other IGF levels were different between exercisers and non-exercisers.  The same held for levels of glucose, insulin, and a measure of insulin resistence (HOMA). 

What does this mean? Previous studies have suggested that the IGF family is associated with premenopausal breast cancer risk – specifically that IGF-1 levels are associated with increased risk of ER+ breast cancer. It may be that the physical activity levels recommended by public health guidelines aren’t intense enough to materially alter levels in the IGF family. Or it may be that exercise needs to be consistent over a longer period of time to see significant changes.

Does this mean we should dismiss the data showing that exercise reduces cancer risk? Not at all. What it does highlight is that randomized trials have great utility for examining very precise questions. This trial studied one specific dose of exercise over a specific number of weeks. The trial can’t tell us what more vigorous activity would have done, or what 60 minutes/day of activity does to the IGF family or what consistent activity over several years does, if anything, to IGF.

Sometimes, randomized trials raise more questions than they answer. Thus, to move science forward, we need BOTH observational and randomized trial evidence.