If you search for statin and cancer on the public science and medicine database and you will find 1,774 articles going back to 1976, so why was there a headline splashed across the newspaper last week? It’s not like we don’t already know about statins. Statins are taken by millions of people around the world to reduce cholesterol by blocking the mevalonate pathway which makes cholesterol (see the figure below). In simple terms, it’s like re-directing a stream of water.
Role of statin in mevalonate pathway
Much of the understanding of the mechanism of action of statins has come from work in animal models, looking at the reduction in circulating cholesterol levels in the blood. We recently investigated the effect of two commonly prescribed statins on a marker of inflammation in white blood cells. In our experiments, we showed that this measured marker of inflammation was decreased in response to both statins, when the cells were first treated with a substance known to mimic the effects of viral infection. By using white blood cells in our experiments, we hypothesized a possible action of statins in blood vessels, to reduce inflammation inside the arteries of people with cardiovascular disease. This is in contrast to the traditional, clinical use of statins to lower lipids in the blood, the amount of circulating ‘fat’ which can be deposited in arteries and cause heart attacks and stroke.
What’s the connection between inflammation and disease?
It has been known for two decades that the underlying pathology in cardiovascular disease is rampant inflammation in the arteries. This inflammation is often due to fatty deposits, which cause red blood cells to clot in the arteries, and turbulence in the blood flow in this area. A number of other cells migrate to the region and release different chemicals, which contribute to the inflammatory reaction, much like you might see if you cut your hand and the wound becomes infected. Other causes of inflammation can be due to viral infections, like influenza. The point about inflammation in the arteries is that it happens over a long time and the markers of it are multiple, therefore, testing for it is still difficult. That is why your doctor will still take a medical history of your health overall, and of your family history.
I mention this because it is likewise known that markers of inflammation, like C-reactive protein for example, in people diagnosed with many kinds of cancer are increased, but only slightly. And two clinical trials looking at the use of statins, the PROVE-IT Study and REVERSAL Trial (reviewed by Salam, 2004) showed a reduction in C-reactive protein in the blood of people taking statins. For scientists, inflammation therefore presents a wonderful environment for experimentation.
Atorvastatin, picture credit
What about statins and cancer?
The author of the report Dr Carol Prives and her team work with p53 a well known tumour suppressor gene found in many but not all cancers, and the research referred to last week is at it’s preliminary stages. Dr Prives reports that the mevalonate pathway is significantly upregulated in tumours containing the p53 mutation. They do not say that statins have an effect on these tumours, merely that the same pathway of action of statins is implicated in p53-containing tumours (Freed-Pastor et al, 2012). This is interesting because it represents another line of research to look at the effect of statins in these tumours. But it should be remembered that cancer cells outside of the human body, such as those used in laboratory experiments, are often derived from people who had cancer and died a long time ago. Their cells have been immortalized and are continually cultured for use in experiments. The disadvantage of this is that sometimes it does not represent the true tumour response. The advantage, however, is that the cells are always the same and experimental data can be compared over time and between laboratories, unlike if we use different people (or animals) each time.
So, there is a long way to go before we can say that millions of lives will be saved by taking statins. And I’m pleased to say that a recent study has found that the number of deaths from heart attacks has halved in the last decade. Although, not all attributed to the use of statins, the results also reflect the drop in smoking, and increased awareness of heart health through good diet and exercise. But, according to one cardiologist, the real importance of statins is longer life, whichever way you look at it.
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