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Association Between Genetically Proxied Inhibition of HMG-CoA Reductase and Epithelial Ovarian Cancer
Open accessAbstract
Importance: Preclinical and epidemiological studies indicate a potential chemopreventive role of statins in epithelial ovarian cancer risk. Objective: To evaluate the association of genetically proxied inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (ie, genetic variants related to lower function of HMG-CoA reductase, target of statins) with epithelial ovarian cancer among the general population and in BRCA1/2 mutation carriers. Design, Setting, and Participants: Single-nucleotide polymorphisms (SNPs) in HMGCR, NPC1L1, and PCSK9 associated with low-density lipoprotein (LDL) cholesterol in a genome-wide association study (GWAS) meta-analysis (N ≤196 475) were used to proxy therapeutic inhibition of HMG-CoA reductase, Niemann-Pick C1-Like 1 (NPC1L1) and proprotein convertase subtilisin/kexin type 9 (PCSK9), respectively. Summary statistics were obtained for these SNPs from a GWAS meta-analysis of case-control analyses of invasive epithelial ovarian cancer in the Ovarian Cancer Association Consortium (OCAC; N = 63 347) and from a GWAS meta-analysis of retrospective cohort analyses of epithelial ovarian cancer among BRCA1/2 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA; N = 31 448). Across the 2 consortia, participants were enrolled between 1973 and 2014 and followed up through 2015. OCAC participants came from 14 countries and CIMBA participants came from 25 countries. SNPs were combined into multi-allelic models and mendelian randomization estimates representing lifelong inhibition of targets were generated using inverse-variance weighted random-effects models. Exposures: Primary exposure was genetically proxied inhibition of HMG-CoA reductase and secondary exposures were genetically proxied inhibition of NPC1L1 and PCSK9 and genetically proxied circulating LDL cholesterol levels. Main Outcomes and Measures: Overall and histotype-specific invasive epithelial ovarian cancer (general population) and epithelial ovarian cancer (BRCA1/2 mutation carriers), measured as ovarian cancer odds (general population) and hazard ratio (BRCA1/2 mutation carriers). Results: The OCAC sample included 22 406 women with invasive epithelial ovarian cancer and 40 941 control individuals and the CIMBA sample included 3887 women with epithelial ovarian cancer and 27 561 control individuals. Median ages for the cohorts ranged from 41.5 to 59.0 years and all participants were of European ancestry. In the primary analysis, genetically proxied HMG-CoA reductase inhibition equivalent to a 1-mmol/L (38.7-mg/dL) reduction in LDL cholesterol was associated with lower odds of epithelial ovarian cancer (odds ratio [OR], 0.60 [95% CI, 0.43-0.83]; P = .002). In BRCA1/2 mutation carriers, genetically proxied HMG-CoA reductase inhibition was associated with lower ovarian cancer risk (hazard ratio, 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 epithelial ovarian cancer. Conclusions and Relevance: Genetically proxied inhibition of HMG-CoA reductase was significantly associated with lower odds of epithelial ovarian cancer. 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.
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“while all CETP inhibitors show modest SBP increasing effects, this appears to be most pronounced for torcetrapib 78 74 .”
From Integrating genomics with biomarkers and therapeutic targets to invigorate cardiovascular drug development (2021) · cites this paper as [74]
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“CETP inhibitors that were primarily developed on the basis that they increased HDL-C (rather than for any effect on cholesterol in apolipoprotein B containing lipoproteins) 74 .”
From Integrating genomics with biomarkers and therapeutic targets to invigorate cardiovascular drug development (2021) · cites this paper as [74]
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Cites
Measuring inconsistency in meta-analyses
Higgins, J. P. T., Thompson, S. G., Deeks, J. J., & Altman, D. G. (2003) · BMJ · doi:10.1136/bmj.327.7414.557 · Cited by 63,139
Bowden, J., Davey Smith, G., & Burgess, S. (2015) · International Journal of Epidemiology · doi:10.1093/ije/dyv080 · Cited by 9,816
Bowden, J., Davey Smith, G., Haycock, P. C., & Burgess, S. (2016) · Genetic Epidemiology · doi:10.1002/gepi.21965 · Cited by 8,922
Genetic studies of body mass index yield new insights for obesity biology
Study, T. L. C., Locke, A. E., The ADIPOGen Consortium, The AGEN-BMI Working Group, The CARDIOGRAMplusC4D Consortium, The CKDGen Consortium, The, G. L. G. C., The, I. C. B. P., The MAGIC Investigators, The MuTHER Consortium, et al. (2015) · Nature · doi:10.1038/nature14177 · Cited by 4,534
Avoiding bias from weak instruments in Mendelian randomization studies
Burgess, S., Thompson, S. G., & CRP CHD Genetics Collaboration (2011) · International Journal of Epidemiology · doi:10.1093/ije/dyr036 · Cited by 3,952
Ovarian cancer statistics, 2018
Torre, L. A., Trabert, B., DeSantis, C. E., Miller, K. D., Samimi, G., Runowicz, C. D., Gaudet, M. M., Jemal, A., & Siegel, R. L. (2018) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.21456 · Cited by 3,492 · cited 1×
“Statistical Analysis Mendelian randomization analysis assumes that the genetic instrument used to proxy a risk factor (1) is associated with the risk factor (“relevance”), (2) does not share a common cause with the outcome (“exchangeability”), and (3) affects the outcome only through the risk factor (“exclusion restri…”
Robust inference in summary data Mendelian randomization via the zero modal pleiotropy assumption
Hartwig, F. P., Davey Smith, G., & Bowden, J. (2017) · International Journal of Epidemiology · doi:10.1093/ije/dyx102 · Cited by 3,485
Willer (2013) · doi:10.1038/ng.2797 · Cited by 2,983
Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers
Kuchenbaecker, K. B., Hopper, J. L., Barnes, D. R., Phillips, K.-A., Mooij, T. M., Roos-Blom, M.-J., Jervis, S., van Leeuwen, F. E., Milne, R. L., Andrieu, N., et al. (2017) · JAMA · doi:10.1001/jama.2017.7112 · Cited by 2,954
Burgess, S., & Thompson, S. G. (2015) · American Journal of Epidemiology · doi:10.1093/aje/kwu283 · Cited by 1,605
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Items 101–129 of 129
Jordan, S. J., & Webb, P. M. (2023) · Oxford University Press eBooks · doi:10.1093/oso/9780192864642.003.0012 · Cited by 2
Fang, S., Yarmolinsky, J., Gill, D., Bull, C. J., Perks, C. M., Smith, G. D., Gaunt, T. R., & Richardson, T. G. (2022) · medRxiv · doi:10.1101/2022.04.18.22274003 · Cited by 2
“6 been applied to suggest that statins may provide additional benefit towards the lowering of ovarian cancer risk [21].”
BackgroundSelf-citationThe emerging role of cholesterol metabolism in gynecologic cancer development and therapy
Liu, H., Zhou, Y., Zhang, J., Miao, L., Wu, Q., Zhu, H., Pan, S., & Zhu, X. (2026) · APOPTOSIS · doi:10.1007/s10495-025-02200-2 · Cited by 1
“In a study of Mendelian randomization, Yamolinsky et al. [31] included 22,406 women with invasive epithelial ovarian cancer and 40,941 control individuals.”
Khalid, Z., Fan, W., Nazir, F., Xing, Y., & Jin, T. (2026) · iNew Medicine · doi:10.1002/inm3.70033 · Cited by 1
Statins as a Combatant for Treatment of Glioblastoma
JAYBHAYE, A. G., Nikam, S. S., Kayande, K., PATIL, P. M., SUROSHE, A. V., ZALTE, P. B., & BHUJBAL, S. A. (2024) · Journal of Drug Delivery and Therapeutics · doi:10.22270/jddt.v14i6.6624 · Cited by 1
“107 Additionally, statin use is associated with a 2-year increase in OS in patients receiving radiation therapy, surgery, and chemotherapy, indicating that statins may help to improve the results of interventions for advanced-stage pancreatic cancer.”
BackgroundZheng, J., Gaunt, T. R., Xu, M., Smith, G. D., & Bi, Y. (2023) · Diabetologia · doi:10.1007/s00125-023-05892-w · Cited by 1
“However, there is little evidence to support an effect of LDL-cholesterol on ovarian cancer [7].”
BackgroundSelf-citationEstimating the effect of lipids on IGF axis and subsequent breast cancer riskPreprint
Tan, V. Y., Bull, C. J., Biernacka, K. M., Teumer, A., Corbin, L. J., Dudding, T., Sanderson, E. C. M., Qi, Q., Kaplan, R. C., Rotter, J. I., et al. (2020) · medRxiv · doi:10.1101/2020.06.04.20122630
Self-citationGenetic epidemiology of endometrial cancer
Kho, P. F. (2021) · Queensland University of Technology · doi:10.5204/thesis.eprints.211383
Liu, S., Feng, S., & Wang, Y. (2023) · SSRN Electronic Journal · doi:10.2139/ssrn.4526509
Zheng, P. F., Rong, J., Zheng, Z., Liu, Z. Y., He, J., & Pan, H. (2023) · SSRN Electronic Journal · doi:10.2139/ssrn.4533597
Zhang, X., & Zou, Y. (2023) · doi:10.22541/au.169581273.38503824/v1
Zheng, J., Lu, J., Qi, J., Yang, Q., Zhao, H., Liu, H., Ye, Y., Xu, M., Xu, Y., Wang, T., et al. (2023) · medRxiv · doi:10.1101/2023.10.10.23296790
“Second, the instruments for SGLT2 were selected using two widely applied pipelines 18,29 .”
MethodSelf-citationAdditional file 1 of A phenome-wide association study of genetically mimicked statins
Li, S., & Schooling, C. M. (2021) · Figshare · doi:10.6084/m9.figshare.14880632
Wang, Z., Wang, M., Zhang, M., Xu, K., Zhang, X., Xie, Y., Zhang, Y., Chang, C., Li, X., Sun, A., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20454541
Wang, Z., Wang, M., Zhang, M., Xu, K., Zhang, X., Xie, Y., Zhang, Y., Chang, C., Li, X., Sun, A., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20454553
Wang, Z., Wang, M., Zhang, M., Xu, K., Zhang, X., Xie, Y., Zhang, Y., Chang, C., Li, X., Sun, A., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20454547
Wang, Z., Wang, M., Zhang, M., Xu, K., Zhang, X., Xie, Y., Zhang, Y., Chang, C., Li, X., Sun, A., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20454550
Bouazzi, M., Zheng, G., Wang, J., Baandrup, L., Hannibal, C. G., Hertzum‐Larsen, R., Sundström, K., & Kjær, S. K. (2025) · Gynecologic Oncology · doi:10.1016/j.ygyno.2025.05.008
Li, Y., Liu, H., Shen, C., Li, J., Liu, F., Huang, K., Gu, D., Li, Y., & Lu, X. (2024) · Figshare · doi:10.6084/m9.figshare.25857516
Wang, Z., Wang, M., Zhang, M., Xu, K., Zhang, X., Xie, Y., Zhang, Y., Chang, C., Li, X., Sun, A., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20454556
Li, Y., Liu, H., Shen, C., Li, J., Liu, F., Huang, K., Gu, D., Li, Y., & Lu, X. (2024) · Figshare · doi:10.6084/m9.figshare.25857598
Wang, Z., Wang, M., Zhang, M., Xu, K., Zhang, X., Xie, Y., Zhang, Y., Chang, C., Li, X., Sun, A., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20454544
Additional file 2 of A phenome-wide association study of genetically mimicked statins
Li, S., & Schooling, C. M. (2021) · Figshare · doi:10.6084/m9.figshare.14880635
Xiao, W., Li, Y., Zhuang, Z., Song, Z., Wang, W., Huang, N., Dong, X. Y., Jia, J., Liu, Z., Zhao, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.25963123
Cylwik, D., Dwornik, R., & Białkowska, K. (2026) · Cancers · doi:10.3390/cancers18030354
“The results confirm that certain polymorphisms are significantly associated with modified ovarian cancer risk, either by increasing or decreasing cancer susceptibility, with similar effects observed in individuals carrying pathogenic variants in BRCA1 or BRCA2 [8,40,41,55,64–67].”
Nutritional and Phytochemical Profile and Potential Anticancer Benefits of Amazonian Exotic Fruits
Lima, T. P. B., de Almeida, C. D. O. R. P., Lemos, I. D. M. L., de Souza, V. R., & Teodoro, A. J. (2025) · Nutrition Reviews · doi:10.1093/nutrit/nuaf307
Yalew, M., Lumsden, A. L., Mulugeta, A., Madakkatel, I., Lee, S., Oehler, M. K., Maenpaa, J. U., & Hyppönen, E. (2026) · Journal of Public Health · doi:10.1093/pubmed/fdag034
Cholesterol in hematological malignancies: metabolism, mechanisms, and clinical implications
Zhang, Y., Yang, M., Yan, S., Li, R., Zheng, Y., Zhang, D., Shang, H., & Fang, W. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1947729
“This activation drives increased fl ux through the mevalonate pathway to meet the substantial demand for membrane components and signalling molecules (52).”
Metabolites and cancer metastasis
Yang, S., Shi, S., Hou, J., Zhang, J., & Su, Z. (2026) · Oncogene · doi:10.1038/s41388-026-03930-6
“Increased mevalonate pathway fl ux and esteri fi cation correlate with higher invasion and outgrowth [131 – 133].”
Metadata
- Authors
- Yarmolinsky, J., Bull, C. J., Vincent, E. E., Robinson, J., Walther, A., Smith, G. D., Lewis, S. J., Relton, C. L., & Martin, R. M.
- Affiliations
- University of Bristol (GB)
- University Hospitals Bristol NHS Foundation Trust (GB)
- Corresponding author
- Martin, Richard M.
- ORCID
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2020-02-18
- Volume
- 323
- Issue
- 7
- Pages
- 646
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC7042851
- OpenAlex
- W3008748669
- Cited by
- 124
- References
- 41
- Citations by year
- 2026: 7 · 2025: 14 · 2024: 24 · 2023: 21 · 2022: 22 · 2021: 24 · 2020: 12
- FWCI
- 7.18
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- public-domain
- Locations
- JAMA (publishedVersion, public-domain)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Explore Bristol Research (publishedVersion, other-oa)
- Funders
- Cancer Research UK (29019, S_3332, 19169)
- Medical Research Council (MC_UU_00011/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Keywords
- epithelial ovarian cancer, HMG-CoA reductase inhibition, statins, chemoprevention, NPC1L1, PCSK9, LDL cholesterol, BRCA1 mutation carriers, BRCA2 mutation carriers, genetic variants, Mendelian randomization, cancer risk, lipid-lowering drugs, Ovarian Cancer Association Consortium
- MeSH terms
- Proprotein Convertase 9, Carcinoma, Ovarian Epithelial, Adult, Female, Humans, Hydroxymethylglutaryl CoA Reductases, Cholesterol, LDL, Middle Aged, Mutation, Ovarian Neoplasms, Retrospective Studies, Risk, Odds Ratio, Case-Control Studies, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Genes, BRCA1, Polymorphism, Single Nucleotide, Genes, BRCA2, Membrane Transport Proteins, Mendelian Randomization Analysis
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