Statin use and risk of prostate cancer and high-grade prostate cancer: results from the REDUCE study

Freedland, Stephen J.; Hamilton, Robert J.; Gerber, Leah; Bañez, Lionel L.; Moreira, Daniel M.; Andriole, Gerald L.; Rittmaster, Roger S.

doi:10.1038/pcan.2013.10

Cited by 54 publications

(48 citation statements)

References 32 publications

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“…Indeed, we observed that statin users had lower PSA levels than nonusers in this study. Randomized trials conducting PSA-independent biopsies at regular intervals may circumvent this potential source of detection bias, and secondary analysis of one such trial reported a null association between statin use and high-grade prostate cancer (24). However, given that trial participants are selected based upon specific eligibility criteria and do not represent a population-based sample, findings from secondary analyses of trials (21,24) may differ from findings reported by population-based studies (19,20), including our own.…”

Section: Discussioncontrasting

confidence: 53%

“…Randomized trials conducting PSA-independent biopsies at regular intervals may circumvent this potential source of detection bias, and secondary analysis of one such trial reported a null association between statin use and high-grade prostate cancer (24). However, given that trial participants are selected based upon specific eligibility criteria and do not represent a population-based sample, findings from secondary analyses of trials (21,24) may differ from findings reported by population-based studies (19,20), including our own. As such, although the potential for screening-related detection biases should be considered, our findings, in addition to those from populations with different PSA screening frequencies (25), support a true association between statin use and prostate cancer aggressiveness.…”

Section: Discussioncontrasting

confidence: 53%

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Statin Use and Prostate Cancer Aggressiveness: Results from the Population-Based North Carolina–Louisiana Prostate Cancer Project

Allott

Farnan

Steck

et al. 2016

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Although statin use has been associated with reduced prostate cancer aggressiveness, the impact of race and patient characteristics on this association is not well understood. We examined the association between statin use and prostate cancer aggressiveness in Caucasians (CA) and African Americans (AA) and explored effect modification by health-seeking behaviors associated with statin use.Methods: Of 1,930 cases from The North Carolina-Louisiana Prostate Cancer Project, 344 (18%) were classified as aggressive based on clinical criteria. Utilizing nonaggressive cases as referent, logistic regression was used to examine the association between statin use and prostate cancer aggressiveness, overall and stratified by race. Smoking and prostate cancer screening were examined as effect modifiers of this association.Results: There was an inverse association between statin use and prostate cancer aggressiveness [OR, 0.74; 95% confidence interval (CI), 0.56-0.96], with comparable effect estimates in

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Section: Discussioncontrasting

confidence: 53%

Section: Discussioncontrasting

confidence: 53%

Statin Use and Prostate Cancer Aggressiveness: Results from the Population-Based North Carolina–Louisiana Prostate Cancer Project

Allott

Farnan

Steck

et al. 2016

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…Herein, we found the link between CAD and PCa risk was unchanged after adjusting for hypercholesterolemia. Furthermore, after adjusting for statins, which some studies suggested are associated with reduced PCa risk, the results remained unchanged, though, in prior analyses from REDUCE, statins were unrelated to PCa risk (22). However, hypercholesterolemia is a crude measure of cholesterol.…”

Section: Discussionmentioning

confidence: 81%

Prostate Cancer Risk in Men with Baseline History of Coronary Artery Disease: Results from the REDUCE Study

Thomas

Gerber

Bañez

et al. 2012

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Coronary artery disease (CAD) and prostate cancer (PCa) are not only common diseases, but share many risk factors. To date, only a few studies have explored the relationship between CAD and PCa risk, with conflicting results.Methods: The four-year REDUCE study tested dutasteride 0.5 mg daily for PCa risk reduction in men with prostate specific antigen (PSA) of 2.5 to 10.0 ng/mL and a negative biopsy. Among men who underwent at least one on-study biopsy (n ¼ 6,729; 82.8%), the association between CAD and overall PCa risk and disease grade was examined with logistic and multinomial logistic regression adjusting for clinicopathologic features, respectively.Results: Overall, 547 men (8.6%) had a history of CAD. Men with CAD were significantly older and had higher body mass index, PSA, and larger prostate volumes and were more likely to have diabetes, hypertension, and hypercholesterolemia and take aspirin and statins. On multivariate analysis, CAD was associated with a 35% increased risk of PCa diagnosis (OR ¼ 1.35, 95% CI: 1.08-1.67, P ¼ 0.007), while elevating risk of both low-(OR ¼ 1.34, 95% CI: 1.05-1.73, P ¼ 0.02) and high-grade disease (OR ¼ 1.34, 95% CI: 0.95-1.88, P ¼ 0.09).Conclusions: In a post hoc hypothesis developing secondary analysis of the REDUCE study, CAD was significantly associated with increased PCa diagnosis.Impact: If confirmed in other studies, this suggests CAD may be a novel PCa risk factor and suggests common shared etiologies. Whether lifestyle changes shown to reduce CAD risk (i.e., weight loss, exercise, cholesterol reduction, etc.) can reduce PCa risk, warrants further study. Cancer Epidemiol Biomarkers Prev; 21(4); 576-81. Ó2012 AACR.

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“…Despite these promising data, other observational studies found no link between statin use and total prostate cancer risk, including a secondary analysis of a randomized trial in men with a negative prostate biopsy who underwent repeat biopsies at 2 years and 4 years 77 , in addition to several cohort studies 5,8,9,11,78–82 . Overall, individual case-control and cohort studies had conflicting findings, but the most recent meta-analysis of these studies from 2012 reported a significant 7% reduction in risk of total prostate cancer in statin users in comparison with nonusers ( P = 0.03) 83 .…”

Section: Epidemiological Evidencementioning

confidence: 98%

The current evidence on statin use and prostate cancer prevention: are we there yet?

et al. 2016

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An increasing amount of data supports an inverse association between statin use and cancer risk. The findings for prostate cancer, particularly advanced disease, are the most promising of all cancers studied. Use of these agents seems to also be associated with improved prostate-cancer-specific survival, particularly in men undergoing radiotherapy, suggesting usefulness of statins in secondary and tertiary prevention. Some study results might be influenced by increased PSA screening and health-conscious behaviour in statin users but these factors are unlikely to completely account for observed beneficial effects. The epidemiological evidence is supported by preclinical studies that show that statins directly inhibit prostate cancer development and progression in cell-based and animal-based models. The antineoplastic effect of statins might arise from a number of cholesterol-mediated and non-cholesterol-mediated mechanisms that affect pathways essential for cancer formation and progression. Understanding these mechanisms is instrumental in drug discovery research for the development of future prostate cancer therapeutics, as well as in designing clinical trials to test a role for statins in prostate cancer prevention. Currently, sufficient data are lacking to support the use of statins for the primary prevention of prostate cancer and further research is clearly warranted. Secondary and tertiary prevention trials in men who have been diagnosed with prostate cancer might soon be performed.

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Statin use and risk of prostate cancer and high-grade prostate cancer: results from the REDUCE study

Abstract: Among men with a negative baseline biopsy and follow-up biopsies largely independent of PSA, statins were not associated with cancer or high-grade cancer.

Cited by 54 publications

References 32 publications

Statin Use and Prostate Cancer Aggressiveness: Results from the Population-Based North Carolina–Louisiana Prostate Cancer Project

Statin Use and Prostate Cancer Aggressiveness: Results from the Population-Based North Carolina–Louisiana Prostate Cancer Project

Prostate Cancer Risk in Men with Baseline History of Coronary Artery Disease: Results from the REDUCE Study

The current evidence on statin use and prostate cancer prevention: are we there yet?

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