If you search for ‘statin and cancer’ on the public science and medicine database you will find 1,774 articles dating back to 1976. So, why was there a dramatic headline splashed across the newspaper last week? It’s not like we don’t already know about statins. They’re taken by millions of people around the world to reduce cholesterol by blocking something called the mevalonate pathway. This is a metabolic pathway involved in cholesterol production. Blocking this pathway reduces the production of cholesterol. This effect is simplified in the figure below. It’s like re-directing a stream of water.
Much of our understanding of of statins has come from work in animal models, looking at the reduction in cholesterol levels in the blood. In the lab I worked in we investigated the effect of two commonly prescribed statins on a protein made in white blood cells, which is a sign of inflammation. We showed that this sign of inflammation was decreased in response to these statins when the cells were treated with a substance known to mimic the effects of infection. As a result of these experiments, we considered another use of statins in blood vessels. They could be used to reduce inflammation inside the arteries of people with cardiovascular disease. The only current accepted, clinical use of statins is to lower the circulating fat (lipids) in the blood, which can be deposited in arteries causing heart attacks and stroke.
What’s the connection between inflammation and disease?
We have known for about twenty years that the underlying pathology in cardiovascular disease is rampant inflammation in the arteries. This is often due to fatty deposits, which cause red blood cells to clot in the arteries. A number of cells migrate to the region and release chemicals, which contribute to the inflammatory reaction, much like you might see if a wound becomes infected. Other causes of inflammation are viral infections, like influenza.Inflammation in the arteries happens over a long time and there are multiple signs in the blood. Testing for it is complex, which is why a doctor will often consider a full medical history when making a diagnosis.
I mention this because it is also known that markers of inflammation, like C-reactive protein in some cancer patients are only slightly increased. 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 people taking statins. For scientists, inflammation presents a wonderful environment for experimentation.
What about statins and cancer?
The author of the report in the newspaper, Dr Carol Prives and her team work with p53 a well known tumour suppressor gene found in many but not all cancers. The research referred to last week is in its very early 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. But, according to one cardiologist, the real importance of statins is longer life, and that’s a good thing, whichever way you look at it.