Statins May Reduce Cancer Risk in Pathway Unrelated to Cholesterol

Cholesterol-lowering statins have been found to potentially reduce the risk of cancer via a pathway that is unrelated to its impact on cholesterol, according to a study published in eLife.

In its use as a cholesterol-lowering drug, statins reduce levels of low-density lipoprotein (LDL) cholesterol through the inhibition of an enzyme called HMG-CoA-reductase (HMGCR). Prior research has also provided evidence that statins may be able to reduce the risk of heart attacks and other cardiovascular diseases, although these results were less clear, according to the current study.

"Previous laboratory studies have suggested that lipids including cholesterol play a role in the development of cancer, and that statins inhibit cancer development," said lead author Paul Carter, MBChB, cardiology academic clinical fellow at the Department of Health and Primary Care, University of Cambridge, in a press release. "However, no trials have been designed to assess the role of statins for cancer prevention in clinical practice. We decided to assess the potential effect of statin therapy on cancer risk using evidence from human genetics."

In order to assess these effects, the researchers investigated genetic variants that mimic the effect of statins by using the Mendelian randomization technique in UK Biobank, which is a large study of residents in the United Kingdom that tracks the diagnosis and treatment of different serious illnesses in the population.

The technique of Mendelian randomization is used by researchers to assess the association between the genetically predicted levels of a risk factor and a disease outcome. The association is then able to help the researchers predict how much the risk factor may cause the outcome.

In this study, which is the first to use Mendelian randomization to analyze lipid subtypes in a range of cancers, the researchers were able to compare the risk of cancer in patients who inherit a genetic predisposition to high or low levels of cholesterol using Mendelian randomization. This allowed the researchers to predict whether lowering cholesterol levels can also reduce cancer risk.

In total, the researchers obtained data on the associations between lipid-related genetic variants with the risk of overall cancer and 22 cancer types for 367,703 individuals from the UK Biobank study, of whom 75,037 had a cancer event.

The results of the analysis demonstrated that variants in the HMGCR gene region, which can act as a proxy for statin treatment, were found to be associated with overall cancer risk. The researchers noted that this suggests that statins have the potential to lower overall cancer risk.

Additionally, those variants in gene regions that are associated with other cholesterol-lowering therapies did not correlate with cancer risk and the genetically predicted LDL cholesterol did not correlate with overall cancer risk as well.

"Taken together, these results suggest that inhibiting HMGCR with statins may help reduce cancer risk though non-lipid lowering mechanisms, and that this role may apply across cancer sites," Carter said in the press release. "This effect may operate through other properties of statins, including dampening down inflammation or reducing other chemicals produced by the same cellular machinery which synthesizes cholesterol."

However, the researchers noted that there remain some limitations to this study. For instance, many cancer types did not result in enough outcome events to completely rule out the potential for moderate causal effects.

"While there is evidence to support our assumption that genetic variants in relevant gene regions can be used as proxies for pharmacological interventions, our findings should be considered with caution until they are confirmed in clinical trials. However, our work highlights that the effectiveness of statins must be urgently evaluated by large clinical trials for potential use in cancer prevention," said senior author of the study Stephen Burgess, PhD, group leader at the Medical Research Council Biostatistics Unit, University of Cambridge, in the press release. "While statins do have some adverse effects, our findings further weight the balance in favor of these drugs reducing the risk of major disease."

REFERENCE

Statins may reduce cancer risk through mechanisms separate to cholesterol. eLife; October 13, 2020. https://www.eurekalert.org/pub_releases/2020-10/e-smr101320.php. Accessed October 16, 2020.