SynthesisBreast cancer research : BCR2022
Associations of genetically proxied inhibition of HMG-CoA reductase, NPC1L1, and PCSK9 with breast cancer and prostate cancer.
Synthesis in Breast cancer research : BCR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 2 syntheses or guidelines pooled it, 43 citations in OpenAlex.
- Review of Mendelian randomization studies on common male-specific diseases.Frontiers in endocrinology · 2025Pooled it
- Risk factors for prostate cancer: An umbrella review of prospective observational studies and mendelian randomization analyses.PLoS medicine · 2024Pooled it
- Emerging roles of the metabolic regulator 3-hydroxy-3-methylglutaryl coenzyme-CoA reductase in human cancers: From biology to therapeutics.Genes & diseases · 2026Review
- PCSK9 and Breast Cancer Survival: A Mendelian Randomization Study.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2026Article
- The association between statin use, genetic variation, and prostate cancer risk.Prostate cancer and prostatic diseases · 2025Article
- PCSK9 Promotes the Malignancy of Triple-negative Breast Cancer Cells by Reducing Cholesterol Levels at the Plasma Membrane to Activate EGFR and HER3.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Modulating NPC1L1 to Potentiate PARP Inhibitor-Induced Ferroptosis and Immune Response in Triple-Negative Breast Cancer.Pharmaceutics · 2025Article
- Genetic association of lipids and lipid-lowering drug target genes with breast cancer.Discover oncology · 2025Article
- The role of statins in breast cancer survivors.Breast cancer research and treatment · 2025Review
- Two-Sample Network Mendelian Randomization and Single-Cell Analysis Reveal the Causal Associations and Underlying Mechanisms Between Antihypertensive Drugs and Kidney Cancer.Journal of Cancer · 2025Article
- Comprehensive Mendelian randomization analysis of low-density lipoprotein cholesterol and multiple cancers.Discover oncology · 2024Article
- Lipid metabolism reprogramming in endometrial cancer: biological functions and therapeutic implications.Cell communication and signaling : CCS · 2024Review
- Cholesterol Metabolism and Urinary System Tumors.Biomedicines · 2024Review
- Atorvastatin lowers breast cancer risk by reversing an early tumorigenic signature.Scientific reports · 2024Article
- The multifaceted role of PCSK9 in cancer pathogenesis, tumor immunity, and immunotherapy.Medical oncology (Northwood, London, England) · 2024Review
- Circulating lipids, lipid-lowering drug targets, and breast cancer risk: Comprehensive evidence from Mendelian randomization and summary data-based Mendelian randomization.Cancer causes & control : CCC · 2024Article
- Causal relationship between lipid-lowering drugs and ovarian cancer, cervical cancer: a drug target mendelian randomization study.BMC cancer · 2024Article
- Prognostic Value ofCancers · 2024Article
- Epithelial-Mesenchymal Transition: A Fundamental Cellular and Microenvironmental Process in Benign and Malignant Prostate Pathologies.Biomedicines · 2024Review
- Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9): from bench to bedside.Signal transduction and targeted therapy · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundPreclinical and epidemiological studies indicate a potential chemopreventive role of low-density lipoprotein cholesterol (LDL-C) -lowering drugs in the risks of breast cancer and prostate cancer, but the causality remains unclear. We aimed to evaluate the association of genetically proxied inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, Niemann-Pick C1-Like 1 (NPC1L1), and proprotein convertase subtilisin/kexin type 9 (PCSK9) with risks of breast cancer and prostate cancer using a two-sample Mendelian randomization (MR) method.
methodsSingle-nucleotide polymorphisms (SNPs) in HMGCR, NPC1L1, and PCSK9 associated with LDL-C in a genome-wide association study (GWAS) meta-analysis from the Global Lipids Genetics Consortium (GLGC; up to 188,577 European individuals) were used to proxy inhibition of HMG-CoA reductase, NPC1L1, and PCSK9. Summary statistics with outcomes were obtained from a GWAS meta-analysis of the Breast Cancer Association Consortium (BCAC; 228,951 European females) and a Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL; 140,254 European males) consortium. SNPs were combined into multiallelic models and MR estimates representing lifelong inhibition of targets were generated using the inverse-variance weighted method.
resultsGenetically proxied inhibition of HMG-CoA reductase (OR: 0.84; 95% CI 0.74-0.95; P = 0.005) and NPC1L1 (OR: 0.72; 95% CI 0.58-0.90; P = 0.005) equivalent to a 1-mmol/L (38.7 mg/dL) reduction in LDL-C was associated with reduced breast cancer risk. There were no significant associations of genetically proxied inhibition of PCSK9 with breast cancer. In contrast, genetically proxied inhibition of PCSK9 (OR: 0.81; 95% CI 0.73-0.90; P < 0.001) but not HMG-CoA reductase and NPC1L1 was negatively associated with prostate cancer. In the secondary analysis, genetically proxied inhibition of HMG-CoA reductase (OR: 0.82; 95% CI 0.71-0.95; P = 0.008) and NPC1L1 (OR: 0.66; 95% CI 0.50-0.86; P = 0.002) was associated with estrogen receptor-positive breast cancer, whereas there was no association of HMG-CoA reductase and NPC1L1 with estrogen receptor-negative breast cancer.
conclusionsGenetically proxied inhibition of HMG-CoA reductase and NPC1L1 was significantly associated with lower odds of breast cancer, while genetically proxied inhibition of PCSK9 was associated with reduced risk of prostate cancer. Further randomized controlled trials are needed to confirm the respective roles of these LDL-C-lowering drugs in breast cancer and prostate cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.