Critical review of cancer risk associated with angiotensin receptor blocker therapy

Wuerzner, Grégoire; Burnier, Michel; Waeber, Bernard

doi:10.2147/vhrm.s13552

Cited by 4 publications

(3 citation statements)

References 69 publications

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“…Angiotensin receptor blockers and angiotensin converting enzyme inhibitors are two of the most commonly used antihypertensive agents. Although study findings are conflicting regarding their relation to cancer risk [ 46 - 49 ], the majority of studies conclude that antihypertensive agents do not initiate cancer development [ 37 , 47 , 50 ], and recent studies even suggest a possible inverse association with cancer incidence [ 48 , 51 ].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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“…Many other retrospective population studies have reported differing effects on cancer risk depending on the cancer type, cohort characteristics, and the RAS inhibitor used. As a result, several meta-analyses have been undertaken (35), again with differing results, which could be due to the nature of the original studies included and inherent publication bias. Aside from the reported effects on cancer risk, many retrospective population studies have also assessed the effect of RAS inhibitors on cancer death.…”

Section: The Renin-angiotensin Systemmentioning

confidence: 99%

Therapeutic Targeting of Cancer Stem Cells via Modulation of the Renin-Angiotensin System

Roth

Wickremesekera

et al. 2019

Front. Oncol.

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Cancer stem cells (CSCs) are proposed to be the cells that initiate tumorigenesis and maintain tumor development due to their self-renewal and multipotency properties. CSCs have been identified in many cancer types and are thought to be responsible for treatment resistance, metastasis, and recurrence. As such, targeting CSCs specifically should result in durable cancer treatment. One potential option for targeting CSCs is by manipulation of the renin-angiotensin system (RAS) and pathways that converge on the RAS with numerous inexpensive medications currently in common clinical use. In addition to its crucial role in cardiovascular and body fluid homeostasis, the RAS is vital for stem cell maintenance and differentiation and plays a role in tumorigenesis and cancer prevention, suggesting that these roles may converge and result in modulation of CSC function by the RAS. In support of this, components of the RAS have been shown to be expressed in many cancer types and have been more recently localized to the CSCs in some tumors. Given these roles of the RAS in tumor development, clinical trials using RAS inhibitors either singly or in combination with other therapies are underway in different cancer types. This review outlines the roles of the RAS, with respect to CSCs, and suggests that the presence of components of the RAS in CSCs could offer an avenue for therapeutic targeting using RAS modulators. Due to the nature of the RAS and its crosstalk with numerous other signaling pathways, a systems approach using traditional RAS inhibitors in combination with inhibitors of bypass loops of the RAS and other signaling pathways that converge on the RAS may offer a novel therapeutic approach to cancer treatment.

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“…and resulted in several commentaries and follow up publications. Many of these papers advised caution in interpretation of the results (Sica 2010;Aalbers 2010;Bloch and Basile 2010;Volpe et al 2011;Madsen 2010;Lombard, Nosworthy, and Albers 2010;Marina and Krakoff 2010;Cohen and Townsend 2011); one solid finding from the meta-analysis was a small increase in risk of cancer with ARB/ACEI combination, but no increase in death (Bangalore et al 2011); many studies concluded that there is no significant risk of ARBs worsening cancer incidence or progression (Collaboration 2011;Pasternak et al 2011;Yoon et al 2011;Cassat et al 2011;"No connection between ARBs and cancer" 2011; Olin, Veverka, and Nuzum 2011;Wuerzner, Burnier, and Waeber 2011;Singh and Bangalore 2012) and one highlighting a reduced risk of cancer with ARB use (Huang et al 2011).…”

Section: Angiotensin Mediators Are Clinically Useful In Cancermentioning

confidence: 99%

6.1.1 Understanding Disease Through Systems Thinking

Smith

2014

INCOSE International Symp

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Angiotensin II is a hormone within the renin‐angiotensin system. Its effects in controlling blood pressure and thirst are universally recognized and well established. In the early part of this millennium we were somewhat puzzled to find that this blood pressure hormone had unforeseen apparently unrelated inflammatory effects and that an imbalance of this system was being implicated as a key driver not only in cardiovascular disease but in many diseases. Systems' thinking reveals a far more profound role for the renin‐angiotensin system in injury sensing, repair and development and provides an explanation for why it is closely associated with the inception and progression of all chronic inflammatory diseases (includes cancers, neurodegenerative diseases, chronic infections and autoimmune conditions). At some point in the future, manipulation of the angiotensin system, when used in synergy with other agents, will undoubtedly be used to far more effectively treat disease. The speed at which this goal is achieved will depend on our ability to adapt our thinking.

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Critical review of cancer risk associated with angiotensin receptor blocker therapy

Cited by 4 publications

References 69 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

Therapeutic Targeting of Cancer Stem Cells via Modulation of the Renin-Angiotensin System

6.1.1 Understanding Disease Through Systems Thinking

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