The Risk of Cancer in Users of Statins

Graaf, Matthijs R.; Beiderbeck, Annette B.; Egberts, Toine C. G.; Richel, Dick J.; Guchelaar, Henk‐Jan

doi:10.1200/jco.2004.02.027

Cited by 476 publications

(377 citation statements)

References 28 publications

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“…However, statins may represent more potent inhibitors of tumour cell proliferation. Recent epidemiologic studies have revealed that statin use reduced the risk of cancer incidence, when different human cancers were studied, including lung cancer (Graaf et al, 2004a). Our data demonstrate that simvastatin may represent a potential new drug to inhibit SCLC proliferation and sensitize tumour cells to chemotherapy.…”

Section: Discussionmentioning

confidence: 61%

Potent inhibition of small-cell lung cancer cell growth by simvastatin reveals selective functions of Ras isoforms in growth factor signalling

Pardo²,

et al. 2005

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The impact of the 3-hydroxy-3methylglutaryl CoA reductase inhibitor simvastatin on human small-cell lung cancer (SCLC) cell growth and survival was investigated. Simvastatin profoundly impaired basal and growth factorstimulated SCLC cell growth in vitro and induced apoptosis. SCLC cells treated with simvastatin were sensitized to the effects of the chemotherapeutic agent etoposide. Moreover, SCLC tumour growth in vivo was inhibited by simvastatin. These responses correlated with the inhibition of stem cell factor (SCF)-stimulated activation of extracellular signal-regulated kinase (Erk), protein kinase B (PKB) and ribosomal S6 kinase by simvastatin. Constitutive activation of the Erk pathway was sufficient to rescue SCLC cell from the effects of simvastatin. The drug did not directly affect activation of c-Kit or its localization to lipid rafts, but in addition to its ability to block Ras membrane localization, it selectively downregulated H-Ras protein levels at the post-translational level. Downregulation of either H-or K-Ras by RNA interference (RNAi) did not impair Erk activation by growth factors, whereas an RNAi specific for N-Ras inhibited activation of Erk, PKB and SCLC cell growth. Together our data demonstrate that inhibiting Ras signalling with simvastatin potently disrupts growth and survival in human SCLC cells.

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Section: Discussionmentioning

confidence: 61%

Potent inhibition of small-cell lung cancer cell growth by simvastatin reveals selective functions of Ras isoforms in growth factor signalling

Pardo²,

et al. 2005

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“…31,51 In a large database analysis, a few years of statin therapy was associated with a 15% proportionally lower rate of cancer-related mortality after adjustment for the potential confounding factors that had been recorded 90 and, in some other observational studies, 136 with as much as a halving in colon cancer incidence and in prostate cancer mortality. 137,138 By contrast, there were small excesses of incident breast cancer in the CARE trial 49 and of incident cancer at all sites in the PROSPER trial among patients who were randomized to receive statin therapy.…”

Section: Lack Of Effects On Non-vascular Mortality and Cancermentioning

confidence: 99%

“…For example, there have been many claims about the benefits of various vitamin supplements based on observational studies 128,129 that have been reliably refuted by large-scale randomized trials. [130][131][132] Similarly, when compared with the results from randomized trials of the effects of treatments for several different cancers, observational studies have generated improbable results despite controlling for comorbidity, extent of disease and many other characteristics that were recorded in detailed databases [133][134][135] (as is also the case for reported associations of statins with lower rates of cancer 90,[136][137][138] ). These findings are consistent with empirical studies in which biases in observational studies were shown to be large enough to conclude falsely that treatment produced benefit or harm, with none of a range of statistical strategies (such as regression analysis or propensity matching) capable of adjusting adequately or predictably for bias.…”

Section: Biases Due To Differences In Underlying Risks Of Health Outcmentioning

confidence: 99%

Interpretation of the evidence for the efficacy and safety of statin therapy

et al. 2016

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General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/pure/about/ebr-terms SummaryThis review is intended to help clinicians, patients and the public make informed decisions about statin therapy for the prevention of heart attacks and strokes. It explains how the evidence that is available from randomized controlled trials yields reliable information about both the efficacy and safety of statin therapy. In addition, it discusses how claims that statins commonly cause adverse effects reflect a failure to recognise the limitations of other sources of evidence about the effects of treatment.Large-scale randomized trial evidence shows that statin therapy reduces the risk of heart attacks, ischaemic strokes and coronary revascularization procedures ("major vascular events") by about one quarter for each mmol/L reduction in low density lipoprotein (LDL) cholesterol during each year (after the first) that it continues to be taken. The absolute benefits of statin therapy depend on an individual's absolute risk of occlusive vascular events and the absolute reduction in LDL cholesterol that is achieved. For example, lowering LDL cholesterol by 2 mmol/L (77 mg/dL) with an effective low-cost statin regimen (e.g. atorvastatin 40 mg daily, costing about £2 per

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“…Interestingly, another large case-control study with cases from a population-based tumor registry reported no overall association of statins with breast cancer incidence but did find that women who had used statins for more than five years had an approximately 30% lower breast cancer incidence than never users [4]. Two other case-control studies observed no association between statin use and breast cancer risk [6,9]. Similarly, four large cohort studies found no association between statin use and risk of breast cancer [3,5,7,8], although one study observed an 18% lower breast cancer incidence with use of lipophilic statins [5].…”

Section: Discussionmentioning

confidence: 99%

“…For example, laboratory studies have shown that lipophilic statins such as simvastatin and fluvastatin inhibit mammary tumor growth by approximately 50% at doses equivalent to those used in humans for reducing cholesterol [2]. Thus far, observational studies of the association between statins and risk of developing breast cancer have yielded mixed results, with the majority finding no association [3][4][5][6][7][8][9][10]. To our knowledge, no studies have examined statin use and breast cancer prognosis.…”

Section: Introductionmentioning

confidence: 99%

Post-diagnosis statin use and breast cancer recurrence in a prospective cohort study of early stage breast cancer survivors

Kwan

Habel

Flick

et al. 2007

Breast Cancer Res Treat

157

138

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PURPOSE-We examined the association between post-diagnosis statin use (3-hydroxy-3-methylglutaryl-coenzyme A [HMG-CoA] inhibitors) and risk of breast cancer recurrence. MATERIALS AND METHODS-The study included 1945 early-stage breast cancer survivors participating in the Life After Cancer Epidemiology (LACE) Study. Women who were diagnosed from 1997 to 2000 and identified from the Kaiser Permanente Northern California (KPNC) Cancer Registry entered the cohort on average two years post-diagnosis. Information on statin use was obtained from the KPNC pharmacy database. A total of 210 breast cancer recurrences were reported and verified by medical record review. Cox proportional hazard models were used to estimate rate ratios (RR) and 95% confidence intervals (CI). RESULTS-The mean duration of statin use in the cohort among those who initiated use postdiagnosis was 1.96 years, and lipophilic statins were mainly used (97.8%). Starting statins after diagnosis was suggestive of a decreased risk of breast cancer recurrence (RR = 0.67; 95% CI: 0.39-1.13). Risk of recurrence decreased with increasing duration of statin use after diagnosis (p linear trend = 0.02).CONCLUSION-Our findings provide initial support for an inverse association between postdiagnosis, lipophilic statin use and risk of breast cancer recurrence.

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The Risk of Cancer in Users of Statins

Abstract: This observational study suggests that statins may have a protective effect against cancer.

Cited by 476 publications

References 28 publications

Potent inhibition of small-cell lung cancer cell growth by simvastatin reveals selective functions of Ras isoforms in growth factor signalling

Potent inhibition of small-cell lung cancer cell growth by simvastatin reveals selective functions of Ras isoforms in growth factor signalling

Interpretation of the evidence for the efficacy and safety of statin therapy

Post-diagnosis statin use and breast cancer recurrence in a prospective cohort study of early stage breast cancer survivors

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