Mo1172 Impact of Statin Therapy on the Long-Term Outcome After Radical Gastrectomy for Gastric Cancer

Nam, Dong Hyuk; Lee, Hyun Jik; Shim, Choong Nam; Park, Jun Chul; Shin, Sung Kwan; Lee, Sang Kil; Lee, Yong Chan; Lee, Hyuk

doi:10.1016/s0016-5085(13)62205-2

Cited by 14 publications

(25 citation statements)

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“…A Korean observational study investigated recurrence‐free survival and all‐cause mortality in 241 patients with Stage 2 and 3 gastric cancer undergoing radical gastrectomy. They observed no overall reduction in all‐cause mortality or recurrence‐free survival in statin users; however, in contrast, there was a marked reduction in all‐cause mortality (HR 0.17; 95% CI, 0.03‐0.88) and recurrence‐free survival (HR 0.37; 95% CI, 0.10‐1.37) in patients using statins for more than 6 months . Finally, an early phase trial from the Netherlands, conducted in 29 patients, showed little evidence of improvement in cancer outcome for patients receiving pravastatin, but this study had limited power.…”

Section: Discussionmentioning

confidence: 97%

“…In addition, several observational studies showed reductions in gastric cancer risk with statin use . Four studies have investigated statin use postgastric cancer diagnosis and survival; however, these were not population‐based, limited by small‐size (largest study contained 244 patients) and were generally conducted in specific subgroups of gastric cancer patients (for instance, Stage 4 patients). Furthermore, results were conflicting, with one study observing an 83% reduction in all‐cause mortality with 6 months of statin use whilst others observed little evidence of improved outcomes …”

Section: Introductionmentioning

confidence: 99%

“…8 In addition, several observational studies showed reductions in gastric cancer risk with statin use. [11][12][13] Four studies [14][15][16][17] have investigated statin use postgastric cancer diagnosis and survival; however, these were not population-based, limited by small-size (largest study contained 244 patients 15 ) and were generally conducted in specific subgroups of gastric cancer patients (for instance, Stage 4 patients 15 ).…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, results were conflicting, with one study 14 observing an 83% reduction in all-cause mortality with 6 months of statin use whilst others observed little evidence of improved outcomes. [15][16][17] We conducted a study using two independent population-based cohorts of patients with gastric cancer to determine the association between statin use and gastric cancer-specific mortality.…”

Section: Introductionmentioning

confidence: 99%

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Statin use and survival in patients with gastric cancer in two independent population‐based cohorts

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Busby

Hughes

et al. 2018

Pharmacoepidemiology and Drug

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Purpose Preclinical studies show statins inhibit pathways involved in gastric cancer progression, with observational studies demonstrating reduced gastric cancer risk in statin users. However, few studies have investigated statin use and survival in gastric cancer. We investigated statin use and survival in two large population‐based gastric cancer cohorts. Methods Patients diagnosed with gastric cancer from 1998 to 2012 were identified from English and Scottish cancer registries. Statin prescriptions were identified from linkages to the UK Clinical Practice Research Datalink in England and the Prescribing Information System in Scotland, and deaths identified from national mortality records. Time‐dependent Cox regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CIs) for cancer‐specific mortality by statin use in multivariate analysis. Meta‐analysis techniques pooled results across the cohorts. Results The combined cohorts contained 3833 patients with gastric cancer and 2392 cancer‐specific deaths. Statin use after diagnosis was associated with reduced cancer‐specific mortality (adjusted HR 0.83; 95% CI, 0.74‐0.92). HRs for less than 1 year and over 1 year of statin use were similar (adjusted HR 0.83; 95% CI, 0.73‐0.94 and adjusted HR 0.83; 95% CI, 0.64‐1.01, respectively). Statin use prior to diagnosis was also associated with reduced cancer‐specific mortality (adjusted HR 0.91; 95% CI, 0.84‐0.98). Conclusions In two independent UK cohorts, there was some evidence that statin use was associated with reduced cancer‐specific mortality. However, these associations were weak in magnitude and did not follow a clear dose response, and we cannot rule out confounding by stage.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Statin use and survival in patients with gastric cancer in two independent population‐based cohorts

Spence

Busby

Hughes

et al. 2018

Pharmacoepidemiology and Drug

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“…[18][19][20][21] Furthermore, as an HMGCR inhibitor, 22 statin is also deemed an inhibitor of carcinogenesis. [23][24][25] Dysregulation of the MVA pathway is commonly observed in glioma, and the related FDPS (farnesyl diphosphate synthase) gene was identified as a new metabolic oncogene and a therapeutic candidate for glioblastoma treatment. 26 Additionally, myc has been shown to mediate its oncogenic effects on glioma tumour-initiating cells partially by affecting MVA metabolism.…”

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confidence: 99%

Artesunate inhibits the mevalonate pathway and promotes glioma cell senescence

Wei

Liu

Chen

et al. 2019

J Cellular Molecular Medi

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Glioma is a common brain malignancy for which new drug development is urgently needed because of radiotherapy and drug resistance. Recent studies have demonstrated that artemisinin (ARS) compounds can display antiglioma activity, but the mechanisms are poorly understood. Using cell lines and mouse models, we investigated the effects of the most soluble ARS analogue artesunate (ART) on glioma cell growth, migration, distant seeding and senescence and elucidated the underlying mechanisms. Artemisinin effectively inhibited glioma cell growth, migration and distant seeding. Further investigation of the mechanisms showed that ART can influence glioma cell metabolism by affecting the nuclear localization of SREBP2 (sterol regulatory element‐binding protein 2) and the expression of its target gene HMGCR (3‐hydroxy‐3‐methylglutaryl coenzyme A reductase), the rate‐limiting enzyme of the mevalonate (MVA) pathway. Moreover, ART affected the interaction between SREBP2 and P53 and restored the expression of P21 in cells expressing wild‐type P53, thus playing a key role in cell senescence induction. In conclusion, our study demonstrated the new therapeutic potential of ART in glioma cells and showed the novel anticancer mechanisms of ARS compounds of regulating MVA metabolism and cell senescence.

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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

116

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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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Mo1172 Impact of Statin Therapy on the Long-Term Outcome After Radical Gastrectomy for Gastric Cancer

Cited by 14 publications

References 0 publications

Statin use and survival in patients with gastric cancer in two independent population‐based cohorts

Statin use and survival in patients with gastric cancer in two independent population‐based cohorts

Artesunate inhibits the mevalonate pathway and promotes glioma cell senescence

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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