Women with naturally lower levels of LDL cholesterol have less risk of ovarian cancer, regardless of mutations in BRCA genes, a genetic analysis study revealed.
The findings suggest a role for cholesterol-lowering statins to prevent the disease, though more research is needed to confirm that, the researchers said.
The study, “Association Between Genetically Proxied Inhibition of HMG-CoA Reductase and Epithelial Ovarian Cancer,” was published in the Journal of the American Medical Association.
Observational studies have found that women who take statins have lower rates of ovarian cancer. And preclinical studies have shown that statins can also inhibit tumor growth and metastasis. However, these findings do not confirm a direct connection between statin therapy and ovarian cancer treatment.
To better understand the connection, researchers at the University of Bristol in the U.K. designed a study to determine if women who had naturally lower levels of cholesterol — mimicking the effects of statins — had a lower ovarian cancer risk.
They examined single nucleotide polymorphisms (SNPs) in genes involved in LDL cholesterol production. SNPs are single changes to the building blocks of the DNA sequence that change a protein’s function; when present in LDL cholesterol-associated genes, they may influence the amount of this cholesterol in a person’s blood.
The researchers studied SNPs associated with lower cholesterol that were found in genes that produce proteins targeted by anti-cholesterol medications.
In particular, they studied five SNPs that lowered the function of the HMG-CoA reductase protein, which is targeted by statins; three SNPs that reduced the functionality of the NPC1L1 protein, which is targeted by ezetimibe (sold as Zetia by Merck); and 11 SNPs that lowered the function of the PCSK9 protein, a target of alirocumab (marketed as Praluent by Sanofi).
The study also included 76 SNPs that were independently associated with LDL cholesterol levels, regardless of genomic position.
The researchers looked at data from 63,347 women included the Ovarian Cancer Association Consortium (OCAC), ages 20 to 100, of whom 22,406 had ovarian cancer. They also examined 31,448 women from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) who carried BRCA mutations, including 3,887 women who had developed epithelial ovarian cancer.
The analysis revealed a significant association between HMG-CoA SNPs and ovarian cancer risk. Specifically, a reduction of one millimole per liter – equivalent to 38.7 milligrams per deciliter (mg/dL) – in LDL cholesterol was significantly associated with a 40% reduced risk of invasive epithelial ovarian cancer. The results were the same for five different disease subtypes.
In those carrying the BRCA1 and BRCA2 mutations, a significantly lower risk of epithelial ovarian cancer was also found in those with lower LDL cholesterol-related HMG-CoA SNPs.
In contrast, SNPs related to NPC1L1 and PCSK9 were not significantly associated with cancer risk in either the OCAC or CIMBA groups.
“Genetically proxied inhibition of HMG-CoA reductase was significantly associated with lower odds of epithelial ovarian cancer,” the scientists said.
“However, these findings do not indicate risk reduction from medications that inhibit HMG-CoA reductase; further research is needed to understand whether there is a similar association with such medications,” they added.
“Our findings open up the possibility of repurposing a cheap drug to help prevent ovarian cancer — especially in women who are at a higher risk,” study co-author Richard Martin, PhD, said in a press release. “It’s incredibly interesting that women whose bodies naturally inhibit the enzyme targeted by statins have a lower risk of ovarian cancer, but we don’t recommend anyone rushes to take statins specifically to reduce ovarian cancer risk because of this study.”
“It’s a promising result, and I hope it sparks more research and trials into statins to demonstrate conclusively whether or not there’s a benefit,” Martin said.