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Causal association between lipid-lowering drugs and cancers: A drug target Mendelian randomization study
Wenjing Ding1, Liangliang Chen2, Jianguo Xia2
1The Second Clinical Medical School, Anhui University of Chinese Medicine, Hefei, Anhui, China.
Medicine
|May 3, 2024
Summary
Lipid-lowering drugs show potential in cancer treatment. Proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors may decrease gastric cancer risk, while 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) inhibitors show mixed effects on various cancers.
Area of Science:
- Pharmacogenomics
- Oncology
- Cardiovascular Pharmacology
Background:
- Emerging evidence suggests lipid-lowering drugs may impact cancer treatment.
- However, the causal relationship between these drugs and cancer risk remains incompletely understood.
Purpose of the Study:
- To investigate the causal associations between proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) inhibitors and the risk of various cancers.
- Utilizing a drug-target Mendelian randomization approach.
Main Methods:
- Employed a drug-target Mendelian randomization analysis.
- Utilized single nucleotide polymorphisms (SNPs) associated with PCSK9 and HMGCR inhibitors.
- Applied five regression methods, with the inverse variance weighted (IVW) method as the primary analysis.
Main Results:
- PCSK9 inhibitors were significantly associated with a decreased risk of gastric cancer (GC) [IVW: OR=0.482].
- Genetic inhibition of HMGCR was significantly correlated with an increased risk of breast cancer (BC), prostate cancer (PC), and skin cancer (SC) [IVW: ORs ranging from 1.266 to 1.617].
- HMGCR inhibitors demonstrated a protective effect against GC and hepatocellular carcinoma (HCC) [IVW: ORs of 0.559 and 0.241, respectively].
Conclusions:
- PCSK9 inhibitors show a significant protective effect against gastric cancer.
- Genetic inhibition of HMGCR is linked to increased risks of breast, prostate, and skin cancers, but HMGCR inhibitors may offer protection against gastric and hepatocellular carcinoma.
- Further clinical trials are warranted to confirm these findings.
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