Statin Use Significantly Improves Overall Survival in High-Grade Endometrial Cancer

Feng, Christine H.; Miller, Charlie M.; Tenney, Meaghan; Lee, Nita K.; Yamada, Satoshi; Hasan, Yasmin

doi:10.1097/igc.0000000000000819

Cited by 21 publications

(28 citation statements)

References 22 publications

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“…Of these, 8 studies were carried out in the United States [29, 31–36, 39], 2 in Israel [30, 38], and 1 in China [37]. The effects of statins on mortality and progression in endometrial cancer [29–33] and ovarian cancer [29, 31, 34–39] were evaluated in 5 and 8 studies, respectively. The Newcastle–Ottawa scale values ranged from 4 to 8 stars: 1 study was awarded 4 stars, 2 studies were award 6 stars, and 6 studies were award 7 or more stars.…”

Section: Resultsmentioning

confidence: 99%

“…Three studies involving 3,460 patients with endometrial cancer evaluated the association between statin use and OS [30, 32, 33]. The pooled data showed improved OS in statin users, though the data supporting this association was not as robust (HR, 0.83; 95% CI, 0.69 to 1.01) (Figure 3).…”

Section: Resultsmentioning

confidence: 99%

“…The pooled data showed improved OS in statin users, though the data supporting this association was not as robust (HR, 0.83; 95% CI, 0.69 to 1.01) (Figure 3). One of the 3 studies also found that hyperlipidemic patients with endometrial cancer who used statins had improved OS compared with those not using statins (HR, 0.42; 95% CI, 0.20 to 0.87) [33]. Five studies involving 1,989 patients with ovarian cancer evaluated the association between statin use and OS [30, 34, 37–39].…”

Section: Resultsmentioning

confidence: 99%

“…Three studies involving 421 patients with endocrine-related gynecologic cancers explored the association between statin use and progression-free survival (PFS) [33, 34, 36]. The pooled data showed that statin use was significantly associated with improved PFS (HR, 0.68; 95% CI, 0.49 to 0.93).…”

Section: Resultsmentioning

confidence: 99%

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Statin use and survival outcomes in endocrine-related gynecologic cancers: A systematic review and meta-analysis

Xie

Huang

et al. 2017

Oncotarget

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Previous studies investigating the association between statin use and survival outcomes in gynecologic cancers have yielded controversial results. We conducted a systematic review and meta-analysis to evaluate the association based on available evidence. We searched the databases of the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and PubMed from inception to January 2017. Studies that evaluated the association between statin use and survival outcomes in gynecologic cancers were included. Pooled hazard ratios (HRs) for overall survival, disease-specific survival and progression-free survival were calculated using a fixed-effects model. A total of 11 studies involving more than 6,920 patients with endocrine-related gynecologic cancers were identified. In a meta-analysis of 7 studies involving 5,449 patients with endocrine-related gynecologic cancers, statin use was linked to improved overall survival (HR, 0.71; 95% confidence interval [CI], 0.63 to 0.80) without significant heterogeneity (I2 = 33.3%). Statin users also had improved disease-specific survival (3 studies, HR, 0.72; 95% CI, 0.58 to 0.90, I2 = 35.1%) and progression-free survival (3 studies, HR, 0.68; 95% CI, 0.49 to 0.93, I2 = 33.6%) in endocrine-related gynecologic cancers. Our findings support that statin use has potential survival benefits for patients with endocrine-related gynecologic cancers. Further large-scale prospective studies are required to validate our findings.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Statin use and survival outcomes in endocrine-related gynecologic cancers: A systematic review and meta-analysis

Xie

Huang

et al. 2017

Oncotarget

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“…Statins inhibit the biosynthesis of geranylgeranyl pyrophosphate (GGPP), the substrate for geranylgeranylation, to induce anti-tumor effects [6,8]. Several clinical trials have indicated that intake of statins can reduce mortality and recurrence in patients with various kinds of cancer [9,10,11,12,13,14]. A combination of statins with first-line chemotherapeutic agents can improve the prognosis of cancer patients [15,16,17].…”

Section: Introductionmentioning

confidence: 99%

Inhibiting HDAC1 Enhances the Anti-Cancer Effects of Statins through Downregulation of GGTase-Iβ Expression

Gan

2017

IJMS

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Hydroxy-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors, namely statins, are potential anti-tumor agents. Previously, we showed that a pan-histone deacetylase (HDAC) inhibitor enhances the anti-tumor effects of the HMG-CoA inhibitor. However, the underlying mechanisms were not fully understood. Cancer cell lines (CAL-27 and SACC-83) were exposed to pan-HDAC inhibitor, or HDAC1 inhibitor, or geranylgeranyl transferase type I (GGTase-I) inhibitor alone or in combination with statin. Cell viability, apoptosis, migration, and invasion were assessed by Cell Count Kit-8, 4′,6-diamidino-2-phenylindole staining, and transwell assay, respectively. A xenograft model was used for assessing tumor growth in vivo. Western blot and real-time PCR were used to assess the expression of genes. We observed that inhibiting HDAC1 could enhance the anti-tumor effects of statins both in vitro and in vivo. Inhibiting HDAC1 blocked the statin-induced upregulation of geranylgeranyl transferase type Iβ subunit (GGTase-Iβ), resulting in an enhancement of the anti-cancer effects of statin. Overexpression of GGTase-Iβ or constitutively active RhoA abolished the enhancement by inhibiting HDAC1 on anti-tumor effects of statins. The HDAC1 inhibitor failed to enhance cytotoxicity in non-tumor primary cells treated with statin. Inhibiting HDAC1 enhanced the anti-cancer effects of statins through downregulation of GGTase-Iβ expression, and thus further inactivation of RhoA. A combination of statin with HDAC1 or GGTase-I inhibitor would be a new strategy for cancer chemotherapy.

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Effects of statins on cancer mortality and progression: A systematic review and meta‐analysis of 95 cohorts including 1,111,407 individuals

Mei

Liang

et al. 2017

Intl Journal of Cancer

115

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Statins have been implicated in the regulation of cell proliferation, apoptosis and tumor progression in cancer patients and statin use at the time of cancer diagnosis has been reported to be associated with reduced cancer risk and improved survival, irrespective of concomitant anti-cancer therapy. A systematic literature search of relevant databases through May 2015 was conducted to identify studies assessing the prognostic impact of statin use on prognostic outcomes in cancer patients. Literature search identified 95 cohort studies that met the inclusion criteria. A meta-analysis of 55 articles showed that statin use was significantly associated with decreased risk of all-cause mortality (HR 0.70, 95% Cl 0.66 to 0.74) compared with nonusers. The observed pooled estimates were retained for cancer-specific mortality (HR 0.60, 95% Cl 0.47 to 0.77), progression-free survival (HR 0.67, 95% Cl 0.56 to 0.81), recurrence-free survial (HR 0.74, 95% Cl 0.65 to 0.83) and disease-free survival (HR 0.53, 95% Cl 0.40 to 0.72). These associations almost remained consistent across those outcomes when stratified by publication type, tumour location, study design, sample size, initiation of statins, disease stage, research country, follow-up duration or research hospital involved. Subgroup analyses according to initiation of statins showed postdiagnosis statin users (HR 0.65, 95% Cl 0.54 to 0.79) gained significantly more recurrence-free survival benefit than prediagnosis statin users (HR 0.86, 95% Cl 0.77 to 0.96) (p for interaction = 0.018). Statin therapy has potential survival benefit for patients with malignancy. Further large-scale prospective studies emphasising survival outcomes of individual cancer type are strongly encouraged.

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Statin Use Significantly Improves Overall Survival in High-Grade Endometrial Cancer

Abstract: Statin use is independently associated with significant improvements in PFS for the overall group and PFS and OS in the hyperlipidemic group.

Cited by 21 publications

References 22 publications

Statin use and survival outcomes in endocrine-related gynecologic cancers: A systematic review and meta-analysis

Statin use and survival outcomes in endocrine-related gynecologic cancers: A systematic review and meta-analysis

Inhibiting HDAC1 Enhances the Anti-Cancer Effects of Statins through Downregulation of GGTase-Iβ Expression

Effects of statins on cancer mortality and progression: A systematic review and meta‐analysis of 95 cohorts including 1,111,407 individuals

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