Abstract:Statin use at diagnosis was not associated with prostate cancer progression in the population-based, minority-enriched HCaP-NC. Greater healthcare engagement, including actively controlling serum cholesterol, may be linked to better prostate cancer-specific outcomes.
“…After carefully reading the titles/abstracts, most studies were excluded because they were reviews (n=11), non-human studies (n=6), or obviously not related with our topic (n=121). After assessing the full-text of 18 potentially relevant articles, we identified 12 eligible studies,9–15,17,23–26 including 13 data sets for analysis; 1 study9 reported the results separately by racial differences. The main reasons for exclusion were as follows: duplicate reports (n=1), no data on exposure (n=1), and no data on outcome of interest (n=4).Figure 1Flow diagram of literature search process.…”
Section: Resultsmentioning
confidence: 99%
“…of casesAge (years)Exposure (no. )Rate of recurrenceAllott et al (black)92016USARMedian: 32.4628Mean: 59.7 (SD: 6.4)TC (46), LDL (46), HDL (188), TG (92)181 (29%)Allott et al (non-black)92016USARMedian: 361020Mean: 62.3 (SD: 5.8)TC (69), LDL (88), HDL (433), TG (182)272 (27%)Allott et al232018USAPMedian: 45.6669Range: 40–79TC (425)138 (21%)Bhindi et al242016CanadaPMedian: 311939Mean: 61.5 (SD: 6.9)HDL (NR), TG (NR)NRKang et al132015KoreaRMedian: 21663Median: 68 (IQR: 62–72)TG (109)66 (10%)Komaru et al122010JapanRMedian: 35173Median: 65 (SD: 5.1)TC (NR)NRMacleod et al102015USARMedian: 411706NRLDL (440), HDL (1174), TG (736)279 (16%)Ohno et al172016JapanRMean: 54.0562Mean: 65....…”
Purpose
The clinical impacts of serum lipid levels on prostate cancer recurrence after radical prostatectomy have been evaluated by several observational studies with conflicting results. We performed the present meta-analysis to summarize the evidence evaluating the role of serum lipid profile in prostate cancer patients.
Methods
We comprehensively searched the PubMed database for potentially relevant studies through January 2019. Pooled hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) for the highest versus the lowest level of serum lipid levels were calculated with the DerSimonian and Laird random-effects model.
Results
A total of 12 eligible studies with 10,978 prostate cancer cases were included in this study. The pooled HRs of prostate cancer recurrence after racial prostatectomy were 0.92 (95% CI 0.73–1.16,
P
=0.462), 0.87 (95% CI 0.56–1.35,
P
=0.535), 1.09 (95% CI 0.92–1.30,
P
=0.320), and 1.01 (95% CI 0.78–1.31,
P
=0.938) for serum total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglyceride, respectively. Sensitivity analysis was conducted by excluding each study sequentially and the results showed that all the summary risk estimates were stable and not influenced by any single study.
Conclusion
The present meta-analysis indicated that serum lipid levels in patients undergoing radical prostatectomy were not associated with prostate cancer recurrence.
“…After carefully reading the titles/abstracts, most studies were excluded because they were reviews (n=11), non-human studies (n=6), or obviously not related with our topic (n=121). After assessing the full-text of 18 potentially relevant articles, we identified 12 eligible studies,9–15,17,23–26 including 13 data sets for analysis; 1 study9 reported the results separately by racial differences. The main reasons for exclusion were as follows: duplicate reports (n=1), no data on exposure (n=1), and no data on outcome of interest (n=4).Figure 1Flow diagram of literature search process.…”
Section: Resultsmentioning
confidence: 99%
“…of casesAge (years)Exposure (no. )Rate of recurrenceAllott et al (black)92016USARMedian: 32.4628Mean: 59.7 (SD: 6.4)TC (46), LDL (46), HDL (188), TG (92)181 (29%)Allott et al (non-black)92016USARMedian: 361020Mean: 62.3 (SD: 5.8)TC (69), LDL (88), HDL (433), TG (182)272 (27%)Allott et al232018USAPMedian: 45.6669Range: 40–79TC (425)138 (21%)Bhindi et al242016CanadaPMedian: 311939Mean: 61.5 (SD: 6.9)HDL (NR), TG (NR)NRKang et al132015KoreaRMedian: 21663Median: 68 (IQR: 62–72)TG (109)66 (10%)Komaru et al122010JapanRMedian: 35173Median: 65 (SD: 5.1)TC (NR)NRMacleod et al102015USARMedian: 411706NRLDL (440), HDL (1174), TG (736)279 (16%)Ohno et al172016JapanRMean: 54.0562Mean: 65....…”
Purpose
The clinical impacts of serum lipid levels on prostate cancer recurrence after radical prostatectomy have been evaluated by several observational studies with conflicting results. We performed the present meta-analysis to summarize the evidence evaluating the role of serum lipid profile in prostate cancer patients.
Methods
We comprehensively searched the PubMed database for potentially relevant studies through January 2019. Pooled hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) for the highest versus the lowest level of serum lipid levels were calculated with the DerSimonian and Laird random-effects model.
Results
A total of 12 eligible studies with 10,978 prostate cancer cases were included in this study. The pooled HRs of prostate cancer recurrence after racial prostatectomy were 0.92 (95% CI 0.73–1.16,
P
=0.462), 0.87 (95% CI 0.56–1.35,
P
=0.535), 1.09 (95% CI 0.92–1.30,
P
=0.320), and 1.01 (95% CI 0.78–1.31,
P
=0.938) for serum total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglyceride, respectively. Sensitivity analysis was conducted by excluding each study sequentially and the results showed that all the summary risk estimates were stable and not influenced by any single study.
Conclusion
The present meta-analysis indicated that serum lipid levels in patients undergoing radical prostatectomy were not associated with prostate cancer recurrence.
“…Statin use was found to be associated with lower risks of primary liver cancer (McGlynn et al, 2015), hepatocellular carcinoma (Kim et al, 2018), HPV-negative squamous cell carcinoma (SCC) of the larynx, hypopharynx, and nasopharynx (Lebo et al, 2018), and subtypes of non-Hodgkin lymphomas including diffuse large B-cell lymphomas and plasma cell lymphomas (Ye et al, 2018), reduced aggressiveness (Allott et al, 2016) and mortality (Yu et al, 2014) of prostate cancer, and lower cancer specific and all-cause mortalities in esophageal cancer (Nguyen et al, 2018). However, statins do not affect survival after colorectal cancer (Hoffmeister et al, 2015) and small-cell lung cancer (Seckl et al, 2017), the risk of pancreatic cancer (Hamada et al, 2018), or the progression of prostate cancer in certain minority-enriched subpopulations (Allott et al, 2018). The type and hydrophilicity of statins, length of statin use, and ethnicity, lifestyle, and preexisting health condition of subjects may have contributed to the diverse outcome in statin and cancer studies—with some but not all studies showing the anticancer effect of statins (Gong et al, 2017).…”
Section: Effects Of Statins On Cancer Growth With Dose-limiting Toxicmentioning
The mevalonate pathway provides sterols for membrane structure and nonsterol intermediates for the post-translational modification and membrane anchorage of growth-related proteins, including the Ras, Rac, and Rho GTPase family. Mevalonate-derived products are also essential for the Hedgehog pathway, steroid hormone signaling, and the nuclear localization of Yes-associated protein and transcriptional co-activator with PDZ-binding motif, all of which playing roles in tumorigenesis and cancer stem cell function. The phosphatidylinositol-4,5-bisphosphate 3-kinase-AKT-mammalian target of rapamycin complex 1 pathway, p53 with gain-of-function mutation, and oncoprotein MYC upregulate the mevalonate pathway, whereas adenosine monophosphate-activated protein kinase and tumor suppressor protein RB are the downregulators. The rate-limiting enzyme, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), is under a multivalent regulation. Sterol regulatory element binding protein 2 mediates the sterol-controlled transcriptional downregulation of HMGCR. UbiA prenyltransferase domain-containing protein-1 regulates the ubiquitination and proteasome-mediated degradation of HMGCR, which is accelerated by 24, 25-dihydrolanosterol and the diterpene geranylgeraniol. Statins, competitive inhibitors of HMGCR, deplete cells of mevalonate-derived intermediates and consequently inhibit cell proliferation and induce apoptosis. Clinical application of statins is marred by dose-limiting toxicities and mixed outcomes on cancer risk, survival and mortality, partially resulting from the statin-mediated compensatory upregulation of HMGCR and indiscriminate inhibition of HMGCR in normal and tumor cells. Tumor HMGCR is resistant to the sterol-mediated transcriptional control; consequently, HMGCR is upregulated in cancers derived from adrenal gland, blood and lymph, brain, breast, colon, connective tissue, embryo, esophagus, liver, lung, ovary, pancreas, prostate, skin, and stomach. Nevertheless, tumor HMGCR remains sensitive to isoprenoid-mediated degradation. Isoprenoids including monoterpenes (carvacrol, L-carvone, geraniol, perillyl alcohol), sesquiterpenes (cacalol, farnesol, β-ionone), diterpene (geranylgeranyl acetone), “mixed” isoprenoids (tocotrienols), and their derivatives suppress the growth of tumor cells with little impact on non-malignant cells. In cancer cells derived from breast, colon, liver, mesothelium, prostate, pancreas, and skin, statins and isoprenoids, including tocotrienols, geraniol, limonene, β-ionone and perillyl alcohol, synergistically suppress cell proliferation and associated signaling pathways. A blend of dietary lovastatin and δ-tocotrienol, each at no-effect doses, suppress the growth of implanted murine B16 melanomas in C57BL6 mice. Isoprenoids have potential as adjuvant agents to reduce the toxicities of statins in cancer prevention or therapy.
“…Findings from several retrospective observational studies indicate that treatment with statins or metformin can reduce prostate-specific antigen (PSA) levels 4–8. Statin use is found to be associated with a lower advanced prostate cancer risk and reduced prostate cancer-specific mortality 9. Statins are potent inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, and are commonly used for treating hyperlipidemia by lowering cholesterol 9,10.…”
Section: Introductionmentioning
confidence: 99%
“…Statin use is found to be associated with a lower advanced prostate cancer risk and reduced prostate cancer-specific mortality 9. Statins are potent inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, and are commonly used for treating hyperlipidemia by lowering cholesterol 9,10. Cholesterol plays a role in steroid androgens that drive prostate growth 11.…”
PurposeTo evaluate the association between the use of statins and/or metformin and patient survival in prostate cancer patients in Taiwan.Subjects and methodsNewly diagnosed prostate cancer patients who had hyperlipidemia and received radiotherapy were identified from the National Health Insurance Research Database 2000–2010. The survival rate was estimated by the Kaplan–Meier method. Univariate and multivariate Cox regression analyses were performed to examine the association of mortality. Sensitivity analysis was performed to assess the risk of mortality in patients with diabetes.ResultsThe study included 567 patients. Patients who used statins or metformin after prostate cancer diagnosis had longer average survival times (9.3 years and 8.1 years, respectively; P=0.001) compared with patients who persistently used or used the medicines prior to cancer diagnosis. Multivariate Cox regression analysis found that patients treated with statins after cancer diagnosis were significantly associated with a lower risk of mortality (aHR =0.24, 95% CI =0.09–0.66) compared to patients who did not use statins during the study period. Patients treated with metformin after cancer diagnosis were significantly associated more with an increased risk of mortality (aHR =6.78, 95% CI =2.45–18.77) compared to patients who did not use metformin during the study period. Sensitivity analysis revealed that the average survival time was similar among different medicine use groups in patients with diabetes.ConclusionThe finding suggests that statins and metformin use after prostate cancer diagnosis may increase survival in patients with hyperlipidemia and radiotherapy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
