Statin Drugs and Risk of Advanced Prostate Cancer

Platz, Elizabeth A.; Leitzmann, Michael F.; Visvanathan, Kala; Rimm, Eric B.; Stampfer, Meir J.; Willett, Walter C.; Giovannucci, Edward

doi:10.1093/jnci/djj499

Cited by 370 publications

(376 citation statements)

References 28 publications

Supporting

Mentioning

353

Contrasting

Unclassified

Order By: Relevance

“…Cholesterol-lowering drugs that inhibit the enzyme HMG-CoA reductase, which catalyzes the ratelimiting step in cholesterol synthesis (these drugs are generically termed 'statins'), have been reported to inhibit cancer incidence or progression in some studies. Although there is much controversy, buttressed by claims and counterclaims, in the various population-based reports of the effects of statins on cancer, recent evidence published by several groups examining large prospective series suggest that prostate cancer progression is likely to be inhibited by long-term cholesterol-lowering therapy (Platz et al, 2006;Mondul et al, 2010). These promising results in humans are in agreement with animal model data, in which cholesterol is raised or lowered and prostate tumor growth thereby promoted or inhibited, respectively (Zhuang et al, 2005;Solomon et al, 2009).…”

supporting

confidence: 54%

The Rafts of the Medusa: cholesterol targeting in cancer therapy

2010

View full text Add to dashboard Cite

supporting

confidence: 54%

The Rafts of the Medusa: cholesterol targeting in cancer therapy

2010

View full text Add to dashboard Cite

“…4,[6][7][8] Supportive evidence for the potential role of cholesterol in prostate cancer development has been provided by observations that cholesterol-lowering drugs (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, commonly known as statins) might be inversely associated with risk of (advanced) prostate cancer. 4,[18][19][20][21] A meta-analysis by Bonovas et al 22 confirmed that use of statins lowers the risk of advanced prostate cancer (relative risk 0.77, 95% CI 0.64-0.93); however, no effect for total prostate cancer risk was found (relative risk 0.95, 95% CI 0.73-1.23). Others proposed that the cholesterol-lowering effects of statins might not be the only reason why these drugs are associated with reduced risk of advanced prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

“…23,24 Furthermore, differences in PSA-screening patterns between statin users and non-users might be responsible for the observed associations. 18,22 As results are conflicting and underlying mechanisms have to be elucidated, further research is needed to evaluate the effects of cholesterollowering drugs on prostate cancer prevention, whereas studies on serum cholesterol and other blood lipids should confirm whether these blood lipids itself are potential risk factors for prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

Blood lipid levels and prostate cancer risk; a cohort study

Kok

Roermund

Aben

et al. 2011

Prostate Cancer Prostatic Dis

View full text Add to dashboard Cite

It has been hypothesized that blood lipid levels might be associated with prostate cancer risk. The aim of the present study was to evaluate the association between serum total cholesterol, highdensity lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides and prostate cancer risk in a cohort study among 2842 Dutch men. By the end of follow-up, 64 incident cases of prostate cancer were identified. Serum total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides were evaluated as potential risk factors for prostate cancer using multivariable Cox proportional hazards regression models. These analyses were restricted to men who never used cholesterol-lowering drugs (2118 men, 43 cases). Higher total and higher LDL cholesterol were significantly associated with an increased risk of prostate cancer (hazards ratios (HR) and 95% confidence interval (CI) per mmol l À1 were 1.39 (95% CI 1.03-1.88) and 1.42 (95% CI 1.00-2.02), respectively). Similar results were observed for aggressive prostate cancer, whereas for nonaggressive prostate cancer a significant association with HDL cholesterol was found (HR 4.28, 95% CI 1.17-15.67). The results of this study suggest that blood lipid levels may influence risk of prostate cancer. However, the exact roles of different cholesterol fractions on prostate cancer aggressiveness should be further evaluated.

show abstract

“…Furthermore, several clinical studies on statin action in prostate cancer have been reported. Platz et al 43 reported that the use of statins reduced the risk of advanced prostate cancer. Mondul et al 44 observed that the use of statins might protect against prostate cancer with poorer pathological characteristics in prostatectomy patients.…”

Section: Discussionmentioning

confidence: 99%

Role of squalene synthase in prostate cancer risk and the biological aggressiveness of human prostate cancer

Fukuma

Matsui

Koike

et al. 2012

Prostate Cancer Prostatic Dis

View full text Add to dashboard Cite

BACKGROUND:We previously conducted a genome-wide linkage analysis of Japanese nuclear families affected with prostate cancer and showed that the susceptibility to prostate cancer was closely linked to D8S550 at 8p23. The role of farnesyl diphosphate farnesyltransferase (FDFT1), which is located under the peak marker D8S550 at 8p23, and squalene synthase, the enzyme encoded by FDFT1, in prostate cancer was studied. METHODS: The association among common variants of FDFT1 with prostate cancer risk, the promoter activities of FDFT1 with different genotypes and the effects of inhibition of squalene synthase were studied, and the FDFT1 transcript levels of human prostate samples were quantified. RESULTS: The A allele of rs2645429 was significantly associated with prostate cancer risk in a Japanese familial prostate cancer population. Rs2645429 was located in the promoter region of FDFT1, and the AA genotype showed significantly increased promoter activity. The knockdown of FDFT1 mRNA expression or squalene synthase inhibition led to a significant decrease in prostate cancer cell proliferation. Additionally, human prostate cancer specimens expressed significantly higher levels of FDFT1 mRNA compared with noncancerous specimens. Finally, aggressive cancers showed higher transcript levels. CONCLUSIONS: FDFT1 and its encoded enzyme, squalene synthase, may play an important role in prostate cancer development and its aggressive phenotypes.

show abstract

Statin Drugs and Risk of Advanced Prostate Cancer

Abstract: In this cohort of male health professionals, use of statin drugs was not associated with risk of prostate cancer overall but was associated with a reduced risk of advanced (especially metastatic or fatal) prostate cancer.

Cited by 370 publications

References 28 publications

The Rafts of the Medusa: cholesterol targeting in cancer therapy

The Rafts of the Medusa: cholesterol targeting in cancer therapy

Blood lipid levels and prostate cancer risk; a cohort study

Role of squalene synthase in prostate cancer risk and the biological aggressiveness of human prostate cancer

Contact Info

Product

Resources

About