A genetic study published in JAMAsuggests long-term statin therapy could reduce the risk for epithelial ovarian cancer (EOC) among the general population and in BRCA1/2 mutation carriers.
The research, funded by Cancer Research UK, evaluated the association of genetically proxied inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGCR)– the target of statins– with EOC.
Single-nucleotide polymorphisms (SNPs) in HMGCR, Niemann-Pick C1-Like 1 (NPC1L1) and proprotein convertase subtilisin/kexin type 9 (PCSK9)– associated with low-density lipoprotein (LDL) cholesterol– were used as proxy for therapeutic inhibition of HMGCR, NPC1L1 and PCSK9.
Summary statistics were obtained for these SNPs from a genome-wide association study (GWAS) meta-analysis of case-control analyses of invasive EOC in the Ovarian Cancer Association Consortium (N=63,347) and from a GWAS meta-analysis of retrospective cohort analyses of EOC among BRCA1/2 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (N=31,448).
In the primary analysis, genetically proxied HMGCR inhibition equivalent to a 1 mmol/L reduction in LDL cholesterol was associated with lower odds of EOC (OR, 0.60; 95% CI, 0.43-0.83; P=.002).
In BRCA1/2 mutation carriers, genetically proxied HMGCR inhibition was associated with lower ovarian cancer risk (HR, 0.69; 95% CI, 0.51-0.93; P=.01).
In secondary analyses, there were no significant associations of genetically proxied inhibition of NPC1L1 (OR, 0.97; 95% CI, 0.53-1.75; P=.91), PCSK9 (OR, 0.98; 95% CI, 0.85-1.13; P=.80) or circulating LDL cholesterol (OR, 0.98; 95% CI, 0.91-1.05; P=.55) with EOC.
However, the authors said these findings do not indicate risk reduction from medications that inhibit HMGCR. They advised that further research is needed to understand whether there is a similar association with such medications.
