UP-2.121: Assessment of Atorvastatin Effectiveness on Serum PSA Level in Hypercholestrolemic Males

Khosropanah, Iradj; Falahatkar, Siavash; Panahandeh, Zahra; Farhat, Babak

doi:10.1016/j.urology.2009.07.340

Cited by 5 publications

(5 citation statements)

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“…Epidemiologic data also suggest that cholesterol increases the risk of PCa 47-50 . Statins are used clinically to reduce LDL levels and they inhibit the rate-limiting step in cholesterol synthesis, but their role in PCa is not fully defined.…”

Section: Discussionmentioning

confidence: 99%

Cholesterol-induced activation of TRPM7 regulates cell proliferation, migration, and viability of human prostate cells

Sun

Sukumaran

Varma³

et al. 2014

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Cholesterol has been shown to promote cell proliferation/migration in many cells; however the mechanism(s) have not yet been fully identified. Here we demonstrate that cholesterol increases Ca2+ entry via the TRPM7 channel, which promoted proliferation of prostate cells by inducing activation of the AKT and/or the ERK pathway. Additionally, cholesterol mediated Ca2+ entry induced calpain activity that showed a decrease in E-cadherin expression, which together could lead to migration of prostate cancer cells. Overexpression of TRPM7 significantly facilitated cholesterol dependent Ca2+ entry, cell proliferation and tumor growth. Whereas, TRPM7 silencing or inhibition of cholesterol synthesis by statin showed a significant decrease in cholesterol-mediated activation of TRPM7, cell proliferation, and migration of prostate cancer cells. Consistent with these results, statin intake was inversely correlated with prostate cancer patients and increase in TRPM7 expression was observed in samples obtained from prostate cancer patients. Altogether, we provide evidence that cholesterol-mediated activation of TRPM7 is important for prostate cancer and have identified that TRPM7 could be essential for initiation and/or progression of prostate cancer.

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Section: Discussionmentioning

confidence: 99%

Cholesterol-induced activation of TRPM7 regulates cell proliferation, migration, and viability of human prostate cells

Sun

Sukumaran

Varma³

et al. 2014

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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“…In small randomized trials, serum PSA has been shown to decline in hypercholesterolemic men after starting on a statin (17). Likewise, several observational studies conducted cross-sectionally (18, 19) or longitudinally (5, 6) found that statin users have lower PSA than nonusers and that serum PSA declines after starting to use a statin.…”

Section: Discussionmentioning

confidence: 99%

Statin Drug Use is Not Associated with Prostate Cancer Risk in Men Who are Regularly Screened

et al. 2014

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Purpose Prospective cohort studies support that statin drug users have a lower risk of aggressive prostate cancer. Whether statin drug use influences risk of screen-detected disease is less clear, possibly because of complex detection biases. Thus, we investigated this association in a setting in which men had low baseline serum PSA concentration and were screened annually Methods We conducted a cohort study of 9,457 men aged ≥55 years old at randomization to the placebo arm of the Prostate Cancer Prevention Trial. The men reported new use of medications quarterly. We estimated the multivariable-adjusted hazard ratio (HR) of prostate cancer (N=574 in 62,192 person-years) for use of a statin drug and duration of use during the trial using Cox proportional hazards regression. Results Over seven years of follow up, use of a statin drug during the trial was not associated with risk of total (HR=1.03, 95% CI 0.82–1.30), lower- (HR=0.96, 95% CI 0.71–1.29), or higher-grade (HR=1.27, 95% CI 0.85–1.90) prostate cancer. Duration of use during follow-up also was not associated with risk of total (P-trend=0.7), lower- (P-trend=0.5), or higher- (P-trend=0.2) grade disease. Conclusion These prospective results do not support the hypothesis that statin drugs protect against prostate cancer in the setting of regular prostate cancer screening.

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“…The inclusion of screen‐detected indolent prostate cancers is a particular concern for exposures related to screening, such as statin use , as residual confounding by screening practices might obscure a protective association. Conversely, statins have been shown to decrease PSA levels, which may alternatively generate a non‐causal inverse association between statins and prostate cancer . Clinically meaningful cancers are less susceptible to these biases, and accordingly, the inverse association between statin use and prostate cancer has been more consistent for advanced/lethal prostate cancers compared to overall prostate cancer .…”

Section: Introductionmentioning

confidence: 99%

Statin use and risk of prostate cancer: Results from the Southern Community Cohort Study

et al. 2015

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Background Epidemiologic studies suggest that statin use may be inversely associated with risk of prostate cancer, but prior studies have focused predominantly on non-Hispanic white populations. Methods We evaluated the association between statin use and prostate cancer risk in the Southern Community Cohort Study (SCCS). Study participants were 32,091 men aged 40-79 at baseline, 67% of whom were non-Hispanic black. Between study enrollment (2002-2009) and December 31, 2010, 570 prostate cancer cases were diagnosed, including 324 low-grade cancers (Gleason score <7 or Gleason pattern 3+4) and 107 high-grade cancers (Gleason score >7 or Gleason pattern 4+3). Analyses of overall prostate cancer were conducted using Cox regression and analyses of grade-specific cancer were conducted using competing risks models. Results Ten percent of non-Hispanic black men and 22% of non-Hispanic white men reported use of statins at study enrollment. As compared to non-use, statin use was associated with a non-significant 14% lower risk of prostate cancer in multivariable models (Hazard Ratio [HR]:0.86; 95% Confidence Interval [CI]:0.63-1.18). This association was stronger for high-grade cancer (HR: 0.62; 95% CI: 0.30, 1.28) than low-grade cancer (HR:0.98; 95% CI:0.65-1.48). Results were similar by race/ethnicity (p-interaction:0.41) and did not vary by history of prostate-specific antigen [PSA] screening (p-interaction:0.65). Conclusions Results suggest no strong association between statin use and prostate cancer risk overall, and further suggest that if a modest protective effect does exist, it does not vary by race/ethnicity and may be restricted to high-grade tumors, although power to detect differences by subgroup was limited.

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UP-2.121: Assessment of Atorvastatin Effectiveness on Serum PSA Level in Hypercholestrolemic Males

Cited by 5 publications

References 0 publications

Cholesterol-induced activation of TRPM7 regulates cell proliferation, migration, and viability of human prostate cells

Cholesterol-induced activation of TRPM7 regulates cell proliferation, migration, and viability of human prostate cells

Statin Drug Use is Not Associated with Prostate Cancer Risk in Men Who are Regularly Screened

Statin use and risk of prostate cancer: Results from the Southern Community Cohort Study

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