Association of Statin Use with the Risk of Incident Prostate Cancer: A Meta-Analysis and Systematic Review

Xu, Meng‐Yao; An, Ye; Liu, Chen‐Qian; Xu, Jin‐Zhou; Zhong, Xing‐Yu; Zeng, Na; Sun, Jian‐Xuan; Xia, Qi‐Dong; Wang, Shaogang

doi:10.1155/2022/7827821

Cited by 6 publications

(4 citation statements)

References 78 publications

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“…[ 42 ] Statins have anti-inflammatory, immunomodulatory effects, and can also induce prostate cancer cell death by promoting autophagy pathways. [ 43 ] Several meta-analyses also support our view, [ 44 , 45 ] and we further found that BT could potentially lower PCa. BT is a part of testosterone that is easily diffused, so it can better reflect the biological activity of testosterone than TT.…”

Section: Discussionsupporting

confidence: 86%

Association between genetically proxied HMGCR inhibition and male reproductive health: A Mendelian randomization study

Yan,

Xu,

et al. 2023

Medicine

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Background: The causal associations between statin use and male sex hormone levels and related disorders have not been fully understood. In this study, we employed Mendelian randomization for the first time to investigate these associations. Methods: In two-sample Mendelian randomization framework, genetic proxies for hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) inhibition were identified as variants in the HMGCR gene that were associated with both levels of gene expression and low density lipoprotein cholesterol (LDL-C). We assessed the causal relationship between HMGCR inhibitor and 5 sex hormone levels/2 male-related diseases. Additionally, we investigated the association between 4 circulating lipid traits and outcomes. The “inverse variance weighting” method was used as the primary approach, and we assessed for potential heterogeneity and pleiotropy. In a secondary analysis, we revalidated the impact of HMGCR on 7 major outcomes using the summary-data-based Mendelian randomization method. Results: Our study found a significant causal association between genetic proxies for HMGCR inhibitor and decreased levels of total testosterone (TT) (LDL-C per standard deviation = 38.7mg/dL, effect = −0.20, 95% confidence interval [CI] = −0.25 to −0.15) and bioavailable testosterone (BT) (effect = −0.15, 95% CI = −0.21 to −0.10). Obesity-related factors were found to mediate this association. Furthermore, the inhibitor were found to mediate a reduced risk of prostate cancer (odds ratio = 0.81, 95%CI = 0.7–0.93) by lowering bioavailable testosterone levels, without increasing the risk of erectile dysfunction (P = .17). On the other hand, there was a causal association between increased levels of LDL-C, total cholesterol, triglycerides (TG) and decreased levels of TT, sex hormone-binding globulin, and estradiol. Conclusions: The use of HMGCR inhibitor will reduce testosterone levels and the risk of prostate cancer without the side effect of erectile dysfunction. LDL-C, total cholesterol, and TG levels were protective factors for TT, sex hormone-binding globulin, and estradiol.

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Section: Discussionsupporting

confidence: 86%

Association between genetically proxied HMGCR inhibition and male reproductive health: A Mendelian randomization study

Yan,

Xu,

et al. 2023

Medicine

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“…The pooled results of 6 randomized control trials (RCTs) and 26 cohort studies indicated a non-significant relationship between statins and prostate cancer occurrence (RR = 0.94, 95% CI: 0.82 to 1.08). Similar results were also achieved from nine case-control studies (OR = 1.03, 95% CI: 0.99 to 1.07) (34). Our results corroborate those of the above meta-analysis, suggesting their findings, statin administration did not affect the OS of RCC patients compared to the control groups (OR = 1.07, 95% CI: 0.77, 1.49, P = 0.68) (35), which contradicts the results of the present meta-analysis.…”

Section: Discussionsupporting

confidence: 82%

The association between statin administration and renal cell carcinoma; a systematic review and meta-analysis

Ramezannezhad

Khosravifarsani

2023

J Renal Inj Prev

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Introduction: Renal cell carcinoma (RCC) is the most prevalent renal cancer in adults, with a rising global incidence. There has long been an ambiguity about the effect of statin administration on the incidence of RCC. The present meta-analysis aims to evaluate the relationship between statin usage and RCC. Materials and Methods: Cochrane, Web of Science, Scopus, and PubMed databases, as well as the Google Scholar search engine, were queried for relevant articles. The data were statistically analyzed by STATA 14 software. The significance level of the tests was considered P<0.05. Results: In 15 reviewed articles, 46 735 subjects used statin, and 673 752 did not. The odds ratio (OR) between statin usage and the risk incidence of RCC was 0.86 (OR: 0.86; 95% CI: 0.63, 1.17) overall and estimated as 0.94 (OR: 0.94; 95% CI: 0.69, 1.28) in males and 0.92 (OR: 0.92; 95% CI: 0.66, 1.28) in females. The odds ratio of statin administration and the incidence risk of RCC was 0.74 (OR: 0.74; 95% CI: 0.37, 1.49) in case-control and 0.96 (OR: 0.96; 95% CI: 0.79, 1.17) in cohort studies. In addition, the impact of statin usage on overall survival (OS) in RCC was 0.65 (HR: 0.65; 95% CI: 0.53, 0.80), and this relationship was statistically significant. However, the effect of statin usage was 0.68 (HR: 0.68; 95% CI: 0.45, 1.02) on progression-free survival (PFS) and 1.24 (OR: 1.24; 95% CI: 0.66, 2.32) on disease progression (DP), and these relationships were statistically non-significant. Conclusion: The OS of RCC patients was 35% higher in statin users than in non-users. However, no relationship between statin usage and the incidence risk of RCC was found. Meta-analysis Registration: This study has been compiled based on the PRISMA checklist, and its protocol was registered on the PROSPERO website (CRD42023393647).

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“…ADT encompasses various treatment modalities aimed at lowering the levels of circulating androgens and blocking their effects on prostate cancer cells [ 22 ]. A recent meta-analysis comprising 41 studies did not find a significant association between statin use and the incidence of prostate cancer [ 23 ]. However, among patients who underwent primary therapies such as RP and/or RT, the use of statins was linked to a 22% reduction in the risk of metastasis and a 24% reduction in the risk of mortality [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Association between Statin Use and Clinical Outcomes in Patients with De Novo Metastatic Prostate Cancer: A Propensity Score-weighted Analysis

Chen,

Liu,

Chang

et al. 2024

World J Mens Health

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Purpose Numerous studies have produced conflicting findings regarding the efficacy of statins in prostate cancer treatment. Our objective was to examine the correlation between statin usage and clinical outcomes in Taiwanese men with de novo metastatic prostate cancer. Materials and Methods We identified patients diagnosed with de novo metastatic prostate cancer from the Chang Gung Research Database spanning the years 2007 to 2020. To minimize confounding bias, we employed the inverse probability of treatment weighting (IPTW) method. Clinical outcomes were assessed using IPTW-adjusted Kaplan-Meier curves. Multivariate Cox proportional hazard regression analysis was utilized to evaluate the association between mortality and clinical factors. Results The study cohort comprised 1,716 statin users and 276 non-users. Patients who used statins exhibited a longer median overall survival (85.4 months compared to 58.2 months; p=0.001) and cancer-specific survival (112.6 months compared to 75.7 months; p<0.001) compared to non-users. The median time to the development of castration-resistant status was similar between statin users and non-users (p=0.069). Multivariable Cox proportional hazards regression analysis, after IPTW adjustment, demonstrated that statin use was associated with improved overall survival. Conclusions Our study indicates that the use of statins following a de novo metastatic prostate cancer diagnosis enhances survival outcomes. However, statins did not appear to delay the onset of castration-resistant status. Further large-scale and long-term studies are warranted to investigate the biological effects of statins in men with prostate cancer.

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Association of Statin Use with the Risk of Incident Prostate Cancer: A Meta-Analysis and Systematic Review

Cited by 6 publications

References 78 publications

Association between genetically proxied HMGCR inhibition and male reproductive health: A Mendelian randomization study

Association between genetically proxied HMGCR inhibition and male reproductive health: A Mendelian randomization study

The association between statin administration and renal cell carcinoma; a systematic review and meta-analysis

Association between Statin Use and Clinical Outcomes in Patients with De Novo Metastatic Prostate Cancer: A Propensity Score-weighted Analysis

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