Statin Use and Incident Prostate Cancer Risk
Statin Use and Incident Prostate Cancer Risk
Background: Statins have known anticarcinogenic effects; evidence for long-term statin use as effective chemoprevention for prostate cancer is inconsistent.
Methods: We conducted a population-based cohort study to examine the association between statin use and risk of prostate cancer using the Database of Clalit Health Services. A total of 66 741 eligible participants were identified at 1 January 2001 and followed through to 31 December 2009. Cox proportional hazard models were used to compute hazard ratios (HRs) of incident prostate cancer associated with statin therapy controling for patients' clinical and sociodemographic characteristics.
Results: A total of 1813 cases of prostate cancer were diagnosed. Statin use was associated with a decreased incidence of prostate cancer, the association was stronger with increasing total dose, hydrophobic statins use and longer periods of treatment. When comparing statin use of over 6 months, this association was strongest for simvastatin (HR 0.51, 95% confidence interval (CI) 0.47–0.56), atorvostatin (HR 0.48, 95% CI 0.33–0.68) and rosuvastatin (HR 0.22, 95% CI 0.08–0.75).
Conclusions: Our findings suggest that prolonged statin use is associated with a reduced risk of prostate cancer; however, this was not true for all types of statin.
Prostate cancer is the second leading cause of cancer deaths among US men, with 186 320 new cases and 28 660 deaths estimated in 2008. Statins lower serum cholesterol levels by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase—the rate-determining enzyme in the mevalonate pathway. In addition to their cholesterol-lowering ability, statins have been shown to inhibit prostate and breast cancer cell proliferation and to induce tumor-specific apoptosis in in vitro studies.
The mechanism whereby statins may inhibit cell proliferation and induce apoptosis in cancer is not fully understood. A number of potential mechanisms have been suggested. The mevalonate pathway has a role in cell-membrane integrity, cell signaling, protein synthesis and cell cycle progression; by blocking this pathway, statins may slow the cancer process. Other suggested mechanisms include activation of Ras and Rho oncoproteins, cholesterol depletion of intracellular lipid rafts and anti-inflammatory effects on prostate tissues.
Studies explaining the association between statin use and prostate cancer have largely been observational and their results have been inconsistent. Some epidemiological studies have reported no overall effect on risk or a decrease in risk. A number of recent studies have consistently reported that statins reduce advanced prostate cancer and aggressive disease. Long-term follow-up of the West of Scotland Coronary Prevention Study, a primary prevention trial involving middle-aged men, showed a significant increase in prostate cancer among those men randomized to pravastatin compared with placebo.
The inconsistencies in previous epidemiological studies have been explained as being due to uncontrolled confounding and ascertainment bias, whereas trials tend to be of short duration, under-powered for the detection of adverse events and susceptible to selection bias. It is also possible that different statins have differing associations with prostate cancer, and inconsistent use of statin type between the studies explains some of the variations in previous studies.
We conducted a population-based cohort study to further examine the association between these widely used medications and prostate cancer risk.
Abstract and Introduction
Abstract
Background: Statins have known anticarcinogenic effects; evidence for long-term statin use as effective chemoprevention for prostate cancer is inconsistent.
Methods: We conducted a population-based cohort study to examine the association between statin use and risk of prostate cancer using the Database of Clalit Health Services. A total of 66 741 eligible participants were identified at 1 January 2001 and followed through to 31 December 2009. Cox proportional hazard models were used to compute hazard ratios (HRs) of incident prostate cancer associated with statin therapy controling for patients' clinical and sociodemographic characteristics.
Results: A total of 1813 cases of prostate cancer were diagnosed. Statin use was associated with a decreased incidence of prostate cancer, the association was stronger with increasing total dose, hydrophobic statins use and longer periods of treatment. When comparing statin use of over 6 months, this association was strongest for simvastatin (HR 0.51, 95% confidence interval (CI) 0.47–0.56), atorvostatin (HR 0.48, 95% CI 0.33–0.68) and rosuvastatin (HR 0.22, 95% CI 0.08–0.75).
Conclusions: Our findings suggest that prolonged statin use is associated with a reduced risk of prostate cancer; however, this was not true for all types of statin.
Introduction
Prostate cancer is the second leading cause of cancer deaths among US men, with 186 320 new cases and 28 660 deaths estimated in 2008. Statins lower serum cholesterol levels by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase—the rate-determining enzyme in the mevalonate pathway. In addition to their cholesterol-lowering ability, statins have been shown to inhibit prostate and breast cancer cell proliferation and to induce tumor-specific apoptosis in in vitro studies.
The mechanism whereby statins may inhibit cell proliferation and induce apoptosis in cancer is not fully understood. A number of potential mechanisms have been suggested. The mevalonate pathway has a role in cell-membrane integrity, cell signaling, protein synthesis and cell cycle progression; by blocking this pathway, statins may slow the cancer process. Other suggested mechanisms include activation of Ras and Rho oncoproteins, cholesterol depletion of intracellular lipid rafts and anti-inflammatory effects on prostate tissues.
Studies explaining the association between statin use and prostate cancer have largely been observational and their results have been inconsistent. Some epidemiological studies have reported no overall effect on risk or a decrease in risk. A number of recent studies have consistently reported that statins reduce advanced prostate cancer and aggressive disease. Long-term follow-up of the West of Scotland Coronary Prevention Study, a primary prevention trial involving middle-aged men, showed a significant increase in prostate cancer among those men randomized to pravastatin compared with placebo.
The inconsistencies in previous epidemiological studies have been explained as being due to uncontrolled confounding and ascertainment bias, whereas trials tend to be of short duration, under-powered for the detection of adverse events and susceptible to selection bias. It is also possible that different statins have differing associations with prostate cancer, and inconsistent use of statin type between the studies explains some of the variations in previous studies.
We conducted a population-based cohort study to further examine the association between these widely used medications and prostate cancer risk.
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