Statins may reduce cancer risk through mechanisms separate t
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Cholesterol-lowering drugs called statins may reduce cancer risk in humans through a pathway unrelated to cholesterol, says a study published today in eLife.

Statins reduce levels of LDL-cholesterol, the so-called 'bad' cholesterol, by inhibiting an enzyme called HMG-CoA-reductase (HMGCR). Clinical trials have previously demonstrated convincing evidence that statins reduce the risk of heart attacks and other cardiovascular diseases. But evidence for the potential effect of statins to reduce the risk of cancer is less clear.

Researchers studied genetic variants that mimic the effect of statins using a technique known as Mendelian randomization in UK Biobank, a large study of UK residents that tracks the diagnosis and treatment of many serious illnesses. Mendelian randomization assesses associations between genetically predicted levels of a risk factor and a disease outcome, in order to predict the extent to which that risk factor causes the outcome. For example, it can compare the risk of cancer in patients who inherit a genetic predisposition to high or low levels of cholesterol, in order to predict whether lowering cholesterol levels will reduce the risk of cancer. This study is the first Mendelian randomization analysis of lipid subtypes for a range of cancers across the human body.

The team obtained associations of lipid-related genetic variants with the risk of overall cancer and 22 cancer types for 367,703 individuals in UK Biobank. In total, 75,037 of these individuals had a cancer event.

Their analysis revealed that variants in the HMGCR gene region, which represent proxies for statin treatment, were associated with overall cancer risk, suggesting that statins could lower overall cancer risk. Interestingly, variants in gene regions that represent other cholesterol-lowering treatments that work differently to statins were not associated with cancer risk, and genetically predicted LDL-cholesterol was not associated with overall cancer risk.

"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," researchers say. "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."