The pleiotropic effects and therapeutic potential of the hydroxy-methyl-glutaryl-CoA reductase inhibitors in malignancies: A comprehensive review

Zeichner, Simon B.; Mihos, Christos G.; Santana, Orlando

doi:10.4103/0973-1482.98967

Cited by 26 publications

(9 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, hypercholesterolemia defined as initiation of treatment with statins, was associated with decreased or neutral cancer risk in both men and women. Statins are by far the most commonly used group of lipid medications, prescribed for elevated total-cholesterol and LDL-cholesterol, and their use has been associated with reduced risk of incident cancer in several, but not all, studies [ 39 – 41 ].…”

Section: Discussionmentioning

confidence: 99%

Associations between metabolic disorders and risk of cancer in Danish men and women – a nationwide cohort study

et al. 2016

View full text Add to dashboard Cite

BackgroundThe prevalence of metabolic disorders is increasing and has been suggested to increase cancer risk, but the relation between metabolic disorders and risk of cancer is unclear, especially in young adults. We investigated the associations between diabetes, hypertension, and hypercholesterolemia on risk of all-site as well as site-specific cancers.MethodsWe consecutively included men and women from nationwide Danish registries 1996–2011, if age 20–89 and without cancer prior to date of entry. We followed them throughout 2012. Metabolic disorders were defined using discharge diagnosis codes and claimed prescriptions. We used time-dependent sex-stratified Poisson regression models adjusted for age and calendar year to assess associations between metabolic disorders, and risk of all-site and site-specific cancer (no metabolic disorders as reference).ResultsOver a mean follow-up of 12.6 (±5.7 standard deviations [SD]) years, 4,826,142 individuals (50.2 % women) with a mean age of 41.4 (±18.9 SD) years had 423,942 incident cancers. Incidence rate ratios (IRRs) of all-site cancer in patients with diabetes or hypertension were highest immediately following diagnosis of metabolic disorder. In women, cancer risk associated with diabetes continued to decline albeit remained significant (IRRs of 1.18–1.22 in years 1–8 following diagnosis). For diabetes in men, and hypertension, IRRs stabilized and remained significantly increased after about one year with IRRs of 1.10-1.13 in men for diabetes, and 1.07–1.14 for hypertension in both sexes. Conversely, no association was observed between hypercholesterolemia (treatment with statins) and cancer risk. The association between hypertension and cancer risk was strongest in young adults aged 20–34 and decreased with advancing age.ConclusionsDiabetes and hypertension were associated with increased risk of all-site cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2122-7) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

Associations between metabolic disorders and risk of cancer in Danish men and women – a nationwide cohort study

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Statins (3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors) reduce age-related heart arrhythmias (Ludman et al ., 2009; Spindler et al ., 2012) and mortality from multiple types of cancer (Zeichner et al ., 2012; Nielsen et al ., 2013). The health benefits of statins stem from reduced protein isoprenylation (Spindler et al ., 2012) and reduced cholesterol biosynthesis (Ludman et al ., 2009).…”

Section: Other Promising Potential Drugs and Drug Targetsmentioning

confidence: 99%

Interventions to Slow Aging in Humans: Are We Ready?

et al. 2015

View full text Add to dashboard Cite

The workshop entitled ‘Interventions to Slow Aging in Humans: Are We Ready?’ was held in Erice, Italy, on October 8–13, 2013, to bring together leading experts in the biology and genetics of aging and obtain a consensus related to the discovery and development of safe interventions to slow aging and increase healthy lifespan in humans. There was consensus that there is sufficient evidence that aging interventions will delay and prevent disease onset for many chronic conditions of adult and old age. Essential pathways have been identified, and behavioral, dietary, and pharmacologic approaches have emerged. Although many gene targets and drugs were discussed and there was not complete consensus about all interventions, the participants selected a subset of the most promising strategies that could be tested in humans for their effects on healthspan. These were: (i) dietary interventions mimicking chronic dietary restriction (periodic fasting mimicking diets, protein restriction, etc.); (ii) drugs that inhibit the growth hormone/IGF-I axis; (iii) drugs that inhibit the mTOR–S6K pathway; or (iv) drugs that activate AMPK or specific sirtuins. These choices were based in part on consistent evidence for the pro-longevity effects and ability of these interventions to prevent or delay multiple age-related diseases and improve healthspan in simple model organisms and rodents and their potential to be safe and effective in extending human healthspan. The authors of this manuscript were speakers and discussants invited to the workshop. The following summary highlights the major points addressed and the conclusions of the meeting.

show abstract

“…β-Hydroxy β-methylglutaryl-CoA (HMG-CoA), also known as 3-hydroxy-3-methylglutaryl-CoA, is an intermediate in the mevalonate and ketogenesis pathways, and its inhibitors (statins) have been used to reduce plasma cholesterol levels for preventing coronary heart disease [3]. Although there have been earlier concerns on the carcinogenicity of statins, such as initiation or promotion of cancers in rodents at concentrations equivalent to those commonly prescribed in humans [4], there has also been growing evidence which suggests that statins could have a chemopreventive effect against cancer [5,6] Although the potential mechanisms of the anti-cancer effect of statin are still elusive, inhibition of cancer cell growth, promotion of apoptotic cell death and inhibition of matrix metalloproteinases are involved in processes such as tumor growth, invasion, and metastasis have been suggested [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Statin and Cancer Mortality and Survival: An Umbrella Systematic Review and Meta-Analysis

Jeong

Lee

Kim

et al. 2020

JCM

View full text Add to dashboard Cite

The aim of this study is to provide an overview and understand the strength of evidence and the extent of potential biases and the validity of claimed associations between the use of statins and cancer mortality or survival. We performed a comprehensive umbrella review of meta-analyses and systematically appraised the relevant meta-analyses of observational studies on the associations between statin use and cancer mortality or survival in various kinds of cancer. We searched the PubMed database and screened the reference list of relevant articles. We obtained the summary effect, 95% confidence interval, heterogeneity, and also examined small study effects and 95% prediction intervals for effect sizes, and the level of evidence was determined from the criteria. Regarding cancer mortality, statin use showed convincing evidence for an association with a reduced cancer-specific mortality rate for colorectal cancer. Four associations with reduced all-cause mortality (for breast cancer, colorectal cancer, endocrine-related gynecological cancer, and ovarian cancer) had a suggestive evidence. Moreover, analyses in nine cancers showed a weak level of evidence, while the remaining 15 did not indicate significant changes in either direction. Although there was a preventive effect of statin on cancer mortality in some cancer types, the evidence supporting the use of statins to reduce cancer mortality or survival was low.

show abstract

The pleiotropic effects and therapeutic potential of the hydroxy-methyl-glutaryl-CoA reductase inhibitors in malignancies: A comprehensive review

Cited by 26 publications

References 84 publications

Associations between metabolic disorders and risk of cancer in Danish men and women – a nationwide cohort study

Associations between metabolic disorders and risk of cancer in Danish men and women – a nationwide cohort study

Interventions to Slow Aging in Humans: Are We Ready?

Statin and Cancer Mortality and Survival: An Umbrella Systematic Review and Meta-Analysis

Contact Info

Product

Resources

About