Statins in the Cause and Prevention of Cancer: Confounding by Indication and Mediation by Rhabdomyolysis and Phosphate Toxicity

被引:1
作者
Brown, Ronald B. [1 ]
机构
[1] Univ Waterloo, Sch Publ Hlth Sci, Waterloo, ON N2L 3G1, Canada
关键词
statin; atherosclerosis; cancer; hypercholesterolemia; hydroxymethylglutaryl-coenzyme A reductase inhibitor; oxysterol; phosphate toxicity; rhabdomyolysis; tumorigenesis; RANDOMIZED PHASE-II; BREAST-CANCER; PROSTATE-CANCER; VITAMIN-D; CLINICAL-TRIALS; RISK-FACTORS; ATHEROSCLEROSIS; ASSOCIATION; DISEASE; PRAVASTATIN;
D O I
10.3390/jcdd11090296
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Statins are drugs used in cardiovascular pharmacotherapy to decrease hypercholesterolemia and lower the risk of atherosclerosis. Statins also increase the risk of rhabdomyolysis, which is often minimized in comparison with large relative risk reductions of cardiovascular disease reported in clinical trials. By contrast, absolute risk reductions of cardiovascular disease are often clinically insignificant and unreported in statin clinical trials. Additionally, cytotoxic effects of statins inhibit cancer cell proliferation and reduce cancer risk, but other studies found that statins are carcinogenic. Due to an inverse association between incidence of cancer and atherosclerosis, the indication to prescribe statins likely biases the association of statins with cancer prevention. Dietary patterns associated with atherosclerosis and cancer contain inverse amounts of cholesterol and phosphate, an essential mineral that stimulates tumorigenesis. Accordingly, lower cancer risk is associated with high dietary cholesterol intake and increased risk of atherosclerosis. Furthermore, serum is exposed to excessive inorganic phosphate that could increase cancer risk as rhabdomyolysis induced by statins releases phosphate from skeletal muscle breakdown. Increased risk of comorbid conditions associated with statins may share the mediating factor of phosphate toxicity. More research is warranted on statins in the cause and prevention of cancer.
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页数:22
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共 176 条
[11]   Curvature, Lipid Packing, and Electrostatics of Membrane Organelles: Defining Cellular Territories in Determining Specificity [J].
Bigay, Joelle ;
Antonny, Bruno .
DEVELOPMENTAL CELL, 2012, 23 (05) :886-895
[12]   Carcinogenesis, cancer therapy and chemoprevention [J].
Blagosklonny, MV .
CELL DEATH AND DIFFERENTIATION, 2005, 12 (06) :592-602
[13]   Interstitial Inorganic Phosphate as a Tumor Microenvironment Marker for Tumor Progression [J].
Bobko, Andrey A. ;
Eubank, Timothy D. ;
Driesschaert, Benoit ;
Dhimitruka, Ilirian ;
Evans, Jason ;
Mohammad, Rahman ;
Tchekneva, Elena E. ;
Dikov, Mikhail M. ;
Khramtsov, Valery V. .
SCIENTIFIC REPORTS, 2017, 7
[14]   Use of statins and breast cancer: A meta-analysis of seven randomized clinical trials and nine observational studies [J].
Bonovas, S ;
Filioussi, K ;
Tsavaris, N ;
Sitaras, NM .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (34) :8606-8612
[15]   Does pravastatin promote cancer in elderly patients? A meta-analysis [J].
Bonovas, Stefanos ;
Sitaras, Nikolaos M. .
CANADIAN MEDICAL ASSOCIATION JOURNAL, 2007, 176 (05) :649-654
[16]  
Boyineni Jerusha, 2020, Oncotarget, V11, P4613, DOI 10.18632/oncotarget.27838
[17]   A RECEPTOR-MEDIATED PATHWAY FOR CHOLESTEROL HOMEOSTASIS [J].
BROWN, MS ;
GOLDSTEIN, JL .
SCIENCE, 1986, 232 (4746) :34-47
[18]  
Brown R. B., 2020, EUROPEAN MED J ONCOL, V8, P114, DOI [10.33590/emjoncol/20-00067, DOI 10.33590/EMJONCOL/20-00067]
[19]   Spontaneous Tumor Regression and Reversion: Insights and Associations with Reduced Dietary Phosphate [J].
Brown, Ronald B. .
CANCERS, 2024, 16 (11)
[20]  
Brown Ronald B, 2024, Medicines (Basel), V11, DOI 10.3390/medicines11020005