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Skriver C, Cronin-Fenton D, Borgquist S, Hansen Viuff J, Alkner S, Rydén L, Lænkholm AV, Manjer J, Bengtsson Y, Frederiksen K, Friis S, Mellemkjær L. Statin use and risk of breast cancer among women with benign breast disease: a Danish nationwide cohort study. Br J Cancer 2025; 132:828-836. [PMID: 40057666 PMCID: PMC12041342 DOI: 10.1038/s41416-025-02974-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 02/06/2025] [Accepted: 02/26/2025] [Indexed: 05/01/2025] Open
Abstract
BACKGROUND Statins have been suggested to protect against breast cancer risk, but the observational evidence is inconclusive. We examined the association between statin use and breast cancer incidence among women at higher risk of breast cancer due to a history of benign breast disease (BBD). METHODS Using Danish registries, we identified cancer-free women aged ≥50 years during 1996-2018 with a history of BBD and no prior statin prescriptions. Using Cox regression, we estimated multivariable-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for invasive breast cancer through 2020 with time-varying statin use defined according to continuity, duration, and intensity (estimated average daily dose), derived from prescription data. RESULTS Among 111,550 women, 7629 were diagnosed with breast cancer during median follow-up of 12.2 years. Overall statin use was not associated with breast cancer incidence (adjusted HR = 0.99; 95% CI, 0.93-1.06), with similar associations observed according to continuity and duration of use. However, long-term (≥10 years), high-intensity statin use was associated with a reduced HR of 0.75 (95% CI, 0.60-0.96). CONCLUSIONS Our findings did not indicate an association for overall statin use with breast cancer incidence among women with BBD. The inverse association with long-term, high-dose statin use requires further evaluation.
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Affiliation(s)
| | - Deirdre Cronin-Fenton
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Signe Borgquist
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
| | - Jakob Hansen Viuff
- Danish Cancer Institute, Copenhagen, Denmark
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Sara Alkner
- Department of Haematology, Oncology, and Radiation Physics, Skåne University Hospital, Lund, Sweden
- Department of Clinical Sciences, Lund, Lund University, Lund, Sweden
| | - Lisa Rydén
- Department of Clinical Sciences, Lund, Lund University, Lund, Sweden
- Department of Surgery, Skåne University Hospital, Malmö, Sweden
| | - Anne-Vibeke Lænkholm
- Department of Surgical Pathology, Zealand University Hospital, Roskilde, Denmark
- Department of Clinical Medicine, Copenhagen University, Copenhagen, Denmark
| | - Jonas Manjer
- Department of Surgery, Skåne University Hospital, Malmö, Sweden
- Department of Clinical Sciences, Malmö, Lund University, Malmö, Sweden
| | - Ylva Bengtsson
- Department of Haematology, Oncology, and Radiation Physics, Skåne University Hospital, Lund, Sweden
- Department of Clinical Sciences, Lund, Lund University, Lund, Sweden
| | | | - Søren Friis
- Danish Cancer Institute, Copenhagen, Denmark
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Tarar ZI, Farooq U, Inayat F, Basida SD, Ibrahim F, Gandhi M, Nawaz G, Afzal A, Chaudhary AJ, Kamal F, Ali AH, Ghouri YA. Statins decrease the risk of hepatocellular carcinoma in metabolic dysfunction-associated steatotic liver disease: A systematic review and meta-analysis. World J Exp Med 2024; 14:98543. [PMID: 39713070 PMCID: PMC11551700 DOI: 10.5493/wjem.v14.i4.98543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Revised: 10/02/2024] [Accepted: 10/24/2024] [Indexed: 10/31/2024] Open
Abstract
BACKGROUND Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease with a significant risk of developing hepatocellular carcinoma (HCC). Recent clinical evidence indicates the potential benefits of statins in cancer chemoprevention and therapeutics. However, it is still unclear if these drugs can lower the specific risk of HCC among patients with MASLD. AIM To investigate the impact of statin use on the risk of HCC development in patients with MASLD. METHODS A systematic review and meta-analysis of all the studies was performed that measured the effect of statin use on HCC occurrence in patients with MASLD. The difference in HCC risk between statin users and non-users was calculated among MASLD patients. We also evaluated the risk difference between lipophilic versus hydrophilic statins and the effect of cumulative dose on HCC risk reduction. RESULTS A total of four studies consisting of 291684 patients were included. MASLD patients on statin therapy had a 60% lower pooled risk of developing HCC compared to the non-statin group [relative risk (RR) = 0.40, 95%CI: 0.31-0.53, I 2 = 16.5%]. Patients taking lipophilic statins had a reduced risk of HCC (RR = 0.42, 95%CI: 0.28-0.64), whereas those on hydrophilic statins had not shown the risk reduction (RR = 0.57, 95%CI: 0.27-1.20). The higher (> 600) cumulative defined daily doses (cDDD) had a 70% reduced risk of HCC (RR = 0.30, 95%CI: 0.21-0.43). There was a 29% (RR = 0.71, 95%CI: 0.55-0.91) and 43% (RR = 0.57, 95%CI: 0.40-0.82) decreased risk in patients receiving 300-599 cDDD and 30-299 cDDD, respectively. CONCLUSION Statin use lowers the risk of HCC in patients with MASLD. The higher cDDD and lipophilicity of statins correlate with the HCC risk reduction.
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Affiliation(s)
- Zahid Ijaz Tarar
- Department of Gastroenterology and Hepatology, University of Missouri, Columbia, MO 65212, United States
| | - Umer Farooq
- Department of Gastroenterology and Hepatology, St. Louis University, St. Louis, MO 63104, United States
| | - Faisal Inayat
- Department of Internal Medicine, Allama Iqbal Medical College, Lahore, Punjab 54550, Pakistan
| | - Sanket D Basida
- Department of Internal Medicine, University of Missouri, Columbia, MO 65212, United States
| | - Faisal Ibrahim
- Department of Internal Medicine, Wexham Park Hospital, Wexham SL24HL, Slough, United Kingdom
| | - Mustafa Gandhi
- Department of Gastroenterology and Hepatology, University of Missouri, Columbia, MO 65212, United States
| | - Gul Nawaz
- Department of Internal Medicine, Allama Iqbal Medical College, Lahore, Punjab 54550, Pakistan
| | - Arslan Afzal
- Department of Hospital Medicine, ECU Health Medical Center, Greenville, NC 27834, United States
| | - Ammad J Chaudhary
- Department of Internal Medicine, Henry Ford Hospital, Detroit, MI 48202, United States
| | - Faisal Kamal
- Department of Gastroenterology and Hepatology, Thomas Jefferson University, Philadelphia, PA 19107, United States
| | - Ahmad H Ali
- Department of Gastroenterology and Hepatology, University of Missouri, Columbia, MO 65212, United States
| | - Yezaz A Ghouri
- Department of Gastroenterology and Hepatology, University of Missouri, Columbia, MO 65212, United States
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Yang S, Ye Z, Ning J, Wang P, Zhou X, Li W, Cheng F. Cholesterol Metabolism and Urinary System Tumors. Biomedicines 2024; 12:1832. [PMID: 39200296 PMCID: PMC11351655 DOI: 10.3390/biomedicines12081832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Revised: 08/06/2024] [Accepted: 08/09/2024] [Indexed: 09/02/2024] Open
Abstract
Cancers of the urinary system account for 13.1% of new cancer cases and 7.9% of cancer-related deaths. Of them, renal cancer, bladder cancer, and prostate cancer are most prevalent and pose a substantial threat to human health and the quality of life. Prostate cancer is the most common malignant tumor in the male urinary system. It is the second most common type of malignant tumor in men, with lung cancer surpassing its incidence and mortality. Bladder cancer has one of the highest incidences and is sex-related, with men reporting a significantly higher incidence than women. Tumor development in the urinary system is associated with factors, such as smoking, obesity, high blood pressure, diet, occupational exposure, and genetics. The treatment strategies primarily involve surgery, radiation therapy, and chemotherapy. Cholesterol metabolism is a crucial physiological process associated with developing and progressing urinary system tumors. High cholesterol levels are closely associated with tumor occurrence, invasion, and metastasis. This warrants thoroughly investigating the role of cholesterol metabolism in urinary system tumors and identifying novel treatment methods for the prevention, early diagnosis, targeted treatment, and drug resistance of urinary system tumors.
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Affiliation(s)
- Songyuan Yang
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan 430060, China; (S.Y.); (Z.Y.); (J.N.); (P.W.); (X.Z.)
| | - Zehua Ye
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan 430060, China; (S.Y.); (Z.Y.); (J.N.); (P.W.); (X.Z.)
| | - Jinzhuo Ning
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan 430060, China; (S.Y.); (Z.Y.); (J.N.); (P.W.); (X.Z.)
| | - Peihan Wang
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan 430060, China; (S.Y.); (Z.Y.); (J.N.); (P.W.); (X.Z.)
| | - Xiangjun Zhou
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan 430060, China; (S.Y.); (Z.Y.); (J.N.); (P.W.); (X.Z.)
| | - Wei Li
- Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, China;
| | - Fan Cheng
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan 430060, China; (S.Y.); (Z.Y.); (J.N.); (P.W.); (X.Z.)
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Okita Y, Sobue T, Zha L, Kitamura T, Iwasaki M, Inoue M, Yamaji T, Tsugane S, Sawada N. Long-term use of anti-cholesterol drugs and cancer risks in a Japanese population. Sci Rep 2024; 14:2896. [PMID: 38316869 PMCID: PMC10844312 DOI: 10.1038/s41598-024-53252-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Accepted: 01/30/2024] [Indexed: 02/07/2024] Open
Abstract
Several studies have investigated the association between the use of anti-cholesterol drugs and cancer risks, of which results have been inconsistent. This study included 67,768 participants from the Japan Public Health Center-based Prospective Study. The data on anti-cholesterol drug use was collected using three questionnaires of the survey conducted every five years. We divided the participants into three groups according to the duration of the anti-cholesterol drug use. Multivariable-adjusted Cox proportional hazard regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). During the 893,009 person-years of follow-up from the 10-year follow-up survey, 8,775 participants (5,387 men and 3,388 women) were newly diagnosed with cancers. The duration of anti-cholesterol drug use was significantly associated with a decreased risk of liver cancer (HR:0.26, 95% CI 0.11-0.64 in > 5 y group) and with an increased risk of pancreatic cancer (HR:1.59, 95% CI 1.03-2.47 in > 5 y group). Moreover, a different trend was observed between men and women in the association with the risk of lung cancer. This study suggested that long-term use of anti-cholesterol drugs may have associations with a decreased incidence of liver cancer and with an increased incidence of pancreatic cancers.
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Affiliation(s)
- Yuki Okita
- Division of Environmental Medicine and Population Sciences, Department of Social Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan
| | - Tomotaka Sobue
- Division of Environmental Medicine and Population Sciences, Department of Social Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan.
| | - Ling Zha
- Division of Environmental Medicine and Population Sciences, Department of Social Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan
| | - Tetsuhisa Kitamura
- Division of Environmental Medicine and Population Sciences, Department of Social Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan
| | - Motoki Iwasaki
- Division of Epidemiology, National Cancer Center Institute for Cancer Control, Chuo-Ku, Tokyo, 104-0045, Japan
- Division of Cohort Research, National Cancer Center Institute for Cancer Control, Chuo-Ku, Tokyo, 104-0045, Japan
| | - Manami Inoue
- Division of Prevention, National Cancer Center Institute for Cancer Control, Chuo-Ku, Tokyo, 104-0045, Japan
| | - Taiki Yamaji
- Division of Epidemiology, National Cancer Center Institute for Cancer Control, Chuo-Ku, Tokyo, 104-0045, Japan
| | - Shoichiro Tsugane
- Division of Cohort Research, National Cancer Center Institute for Cancer Control, Chuo-Ku, Tokyo, 104-0045, Japan
- National Institute of Health and Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition, Shinjuku-Ku, Tokyo, 162-8636, Japan
| | - Norie Sawada
- Division of Cohort Research, National Cancer Center Institute for Cancer Control, Chuo-Ku, Tokyo, 104-0045, Japan
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Khaghani A, Kasiri K, Heidari-Soureshjani S, Sherwin CMT, Mardani-Nafchi H. A Systematic Review and Meta-analysis of the Relationship between Statin Intake and Esophageal Cancer. Anticancer Agents Med Chem 2024; 24:1029-1037. [PMID: 38812422 DOI: 10.2174/0118715206292712240522043350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Revised: 04/14/2024] [Accepted: 04/25/2024] [Indexed: 05/31/2024]
Abstract
BACKGROUND Esophageal cancer is a malignant tumor with a low survival rate. Statins, commonly prescribed for their lipid-lowering effects, have been suggested to possess potential chemopreventive properties against various cancers, including esophageal cancer. OBJECTIVES This systematic review studied the association between statin intake and esophageal cancer. METHODS To conduct this systematic review and meta-analysis, we reviewed studies published between 1980 and June 2023 in Web of Science (WOS), Embase, MEDLINE/PubMed, Scopus, and Cochrane Library databases according to the PRISMA guidelines. Data extraction, quality assessment, and statistical analyses were performed using predefined protocols. We used various statistical tests conducted by Stata statistical software. Statistical significance was considered significant at p < 0.05. RESULTS Twenty-one studies were collected and analyzed. The meta-analysis demonstrated that the odds ratio (OR) of esophageal cancer in patients treated with statins was 0.65 (95% CI: 0.57-0.75, p < 0.001) compared to the non-receiving group. The ORs for case-control and cohort studies were 0.67 (95% CI:0.54-0.83, p < 0.001) and 0.62 (95% CI:0.55-0.71, p < 0.001), respectively. The investigation into the relationship between the statins intake and the incidence of esophageal cancer did not reveal any indication of publication bias according to both Begg's test (p = 0.966) and Egger's test (p = 0.113). CONCLUSION The results revealed that the odds of esophageal cancer in patients treated with statins decreased by 35% compared to patients not treated with statins. However, further well-designed prospective studies are needed to validate these findings and understand the underlying mechanisms of statins in preventing esophageal cancer.
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Affiliation(s)
- Armin Khaghani
- Skin Diseases and Leishmaniasis Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Karamali Kasiri
- Department of Pediatrics, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | | | - Catherine M T Sherwin
- Pediatric Clinical Pharmacology and Toxicology, Department of Pediatrics, Wright State University Boonshoft School of Medicine, Dayton Children's Hospital, One Children's Plaza, Dayton, Ohio, USA
| | - Hossein Mardani-Nafchi
- Department of Pharmacology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Li H, Zhang L, Yang F, Feng X, Fu R, Zhao R, Li X, Li H. Lipid-lowering drugs affect lung cancer risk via sphingolipid metabolism: a drug-target Mendelian randomization study. Front Genet 2023; 14:1269291. [PMID: 38034491 PMCID: PMC10687161 DOI: 10.3389/fgene.2023.1269291] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 11/02/2023] [Indexed: 12/02/2023] Open
Abstract
Background: The causal relationship between lipid-lowering drug (LLD) use and lung cancer risk is controversial, and the role of sphingolipid metabolism in this effect remains unclear. Methods: Genome-wide association study data on low-density lipoprotein (LDL), apolipoprotein B (ApoB), and triglycerides (TG) were used to develop genetic instrumental variables (IVs) for LLDs. Two-step Mendelian randomization analyses were performed to examine the causal relationship between LLDs and lung cancer risk. The effects of ceramide, sphingosine-1-phosphate (S1P), and ceramidases on lung cancer risk were explored, and the proportions of the effects of LLDs on lung cancer risk mediated by sphingolipid metabolism were calculated. Results: APOB inhibition decreased the lung cancer risk in ever-smokers via ApoB (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.70-0.92, p = 0.010), LDL (OR 0.82, 95% CI 0.71-0.96, p = 0.040), and TG (OR 0.63, 95% CI 0.46-0.83, p = 0.015) reduction by 1 standard deviation (SD), decreased small-cell lung cancer (SCLC) risk via LDL reduction by 1 SD (OR 0.71, 95% CI 0.56-0.90, p = 0.016), and decreased the plasma ceramide level and increased the neutral ceramidase level. APOC3 inhibition decreased the lung adenocarcinoma (LUAD) risk (OR 0.60, 95% CI 0.43-0.84, p = 0.039) but increased SCLC risk (OR 2.18, 95% CI 1.17-4.09, p = 0.029) via ApoB reduction by 1 SD. HMGCR inhibition increased SCLC risk via ApoB reduction by 1 SD (OR 3.04, 95% CI 1.38-6.70, p = 0.014). The LPL agonist decreased SCLC risk via ApoB (OR 0.20, 95% CI 0.07-0.58, p = 0.012) and TG reduction (OR 0.58, 95% CI 0.43-0.77, p = 0.003) while increased the plasma S1P level. PCSK9 inhibition decreased the ceramide level. Neutral ceramidase mediated 8.1% and 9.5% of the reduced lung cancer risk in ever-smokers via ApoB and TG reduction by APOB inhibition, respectively, and mediated 8.7% of the reduced LUAD risk via ApoB reduction by APOC3 inhibition. Conclusion: We elucidated the intricate interplay between LLDs, sphingolipid metabolites, and lung cancer risk. Associations of APOB, APOC3, and HMGCR inhibition and LPL agonist with distinct lung cancer risks underscore the multifaceted nature of these relationships. The observed mediation effects highlight the considerable influence of neutral ceramidase on the lung cancer risk reduction achieved by APOB and APOC3 inhibition.
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Affiliation(s)
- Honglin Li
- First Clinical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Lei Zhang
- First Clinical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Feiran Yang
- Department of Oncology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Xiaoteng Feng
- Department of Cardiology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Rong Fu
- First Clinical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Ruohan Zhao
- Department of Oncology, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xiurong Li
- Department of Oncology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Huijie Li
- Department of Oncology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
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Piekuś-Słomka N, Mocan LP, Shkreli R, Grapă C, Denkiewicz K, Wesolowska O, Kornek M, Spârchez Z, Słomka A, Crăciun R, Mocan T. Don't Judge a Book by Its Cover: The Role of Statins in Liver Cancer. Cancers (Basel) 2023; 15:5100. [PMID: 37894467 PMCID: PMC10605163 DOI: 10.3390/cancers15205100] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 10/16/2023] [Accepted: 10/20/2023] [Indexed: 10/29/2023] Open
Abstract
Statins, which are inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, are an effective pharmacological tool for lowering blood cholesterol levels. This property makes statins one of the most popular drugs used primarily to prevent cardiovascular diseases, where hyperlipidemia is a significant risk factor that increases mortality. Nevertheless, studies conducted mainly in the last decade have shown that statins might prevent and treat liver cancer, one of the leading causes of cancer-related mortality worldwide. This narrative review summarizes the scientific achievements to date regarding the role of statins in liver tumors. Molecular biology tools have revealed that cell growth and proliferation can be inhibited by statins, which further inhibit angiogenesis. Clinical studies, supported by meta-analysis, confirm that statins are highly effective in preventing and treating hepatocellular carcinoma and cholangiocarcinoma. However, this effect may depend on the statin's type and dose, and more clinical trials are required to evaluate clinical effects. Moreover, their potential hepatotoxicity is a significant caveat for using statins in clinical practice. Nevertheless, this group of drugs, initially developed to prevent cardiovascular diseases, is now a key candidate in hepato-oncology patient management. The description of new drug-statin-like structures, e.g., with low toxicity to liver cells, may bring another clinically significant improvement to current cancer therapies.
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Affiliation(s)
- Natalia Piekuś-Słomka
- Department of Inorganic and Analytical Chemistry, Nicolaus Copernicus University in Toruń, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Jurasza 2, 85-089 Bydgoszcz, Poland;
| | - Lavinia Patricia Mocan
- Department of Histology, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania;
| | - Rezarta Shkreli
- Department of Pharmacy, Faculty of Medical Sciences, Aldent University, 1001-1028 Tirana, Albania;
| | - Cristiana Grapă
- Department of Physiology, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania;
| | - Kinga Denkiewicz
- Department of Pathophysiology, Nicolaus Copernicus University in Toruń, Ludwik Rydygier Collegium Medicum in Bydgoszcz, 85-094 Bydgoszcz, Poland; (K.D.); (O.W.); (A.S.)
| | - Oliwia Wesolowska
- Department of Pathophysiology, Nicolaus Copernicus University in Toruń, Ludwik Rydygier Collegium Medicum in Bydgoszcz, 85-094 Bydgoszcz, Poland; (K.D.); (O.W.); (A.S.)
| | - Miroslaw Kornek
- Department of Internal Medicine I, University Hospital Bonn of the Rheinische Friedrich-Wilhelms-University, 53127 Bonn, Germany;
| | - Zeno Spârchez
- 3rd Medical Department, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400162 Cluj-Napoca, Romania;
| | - Artur Słomka
- Department of Pathophysiology, Nicolaus Copernicus University in Toruń, Ludwik Rydygier Collegium Medicum in Bydgoszcz, 85-094 Bydgoszcz, Poland; (K.D.); (O.W.); (A.S.)
| | - Rareș Crăciun
- 3rd Medical Department, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400162 Cluj-Napoca, Romania;
- Department of Gastroenterology, “Octavian Fodor” Institute for Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
| | - Tudor Mocan
- Department of Gastroenterology, “Octavian Fodor” Institute for Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
- UBBMed Department, Babeș-Bolyai University, 400349 Cluj-Napoca, Romania
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Chen Y, Zhang J, Zhang Y, Zhu L. Effect of statin use on risk and mortality of gastric cancer: a meta-analysis. Anticancer Drugs 2023; 34:901-909. [PMID: 37227032 DOI: 10.1097/cad.0000000000001524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/26/2023]
Abstract
The effect of statins on gastric cancer risk is still controversial. And studies on the association between statins and gastric cancer mortality are very limited. Therefore, we conducted this systemic review and meta-analysis to evaluate the association between the use of statin and gastric cancer. Searched studies were published before November 2022. Odds ratios (ORs)/relative risks (RRs) or hazard ratios (HRs) and their 95% confidence intervals (CIs) were computed using STATA 12.0 software. The study showed that the statin use group showed a significantly lower risk of gastric cancer, compared to no statin use group (OR/RR, 0.74; 95% CI: 0.67-0.80, P < 0.001). The study showed that the statin use group showed significantly lower all-cause mortality and cancer-specific mortality of gastric cancer, compared to no statin use group (all-cause mortality: HR, 0.70; 95% CI: 0.52-0.95, P = 0.021; cancer-specific mortality: HR, 0.70; 95% CI: 0.58-0.84, P < 0.001). Overall, results from this meta-analysis showed the protective effect of statins exposure on the risk and prognosis of gastric cancer; however, we still need more well designed, large-scale studies and randomized clinical trials to pinpoint the effect of statins on gastric cancer in future clinical practice.
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Affiliation(s)
- Yi Chen
- General Practice Ward/International Medical Center Ward, General Practice Medical Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
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Symvoulidis P, Tsioutis C, Zamboglou C, Agouridis AP. The Effect of Statins on the Incidence and Prognosis of Bladder Cancer: A Systematic Review and Meta-Analysis. Curr Oncol 2023; 30:6648-6665. [PMID: 37504348 PMCID: PMC10378493 DOI: 10.3390/curroncol30070488] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Revised: 06/28/2023] [Accepted: 07/10/2023] [Indexed: 07/29/2023] Open
Abstract
BACKGROUND Statins are widely used due to their ability to lower plasma cholesterol and offer protection from the effects of atherosclerosis. However, their role in urology and specifically bladder cancer remains unclear. We aimed to systematically address this issue in the literature and determine any possible effects of statin therapy on bladder cancer. METHODS We searched MEDLINE (PubMed) and Cochrane Library databases for records up to 26 March 2023, for studies evaluating the effects of statins on urinary bladder cancer (UBC). We included all randomized controlled trials (RCTs), cohorts, and case-control studies that were conducted on the adult population. PROSPERO registration number: CRD42023407795. RESULTS Database searches returned 2251 reports, and after thorough investigation and assessment for eligibility, 32 reports were included in the analysis. Of them, 4 were RCTs, 6 were case-control studies, and 22 were cohort studies. Our qualitative analysis demonstrated no association between statin administration and UBC local control, recurrence, survival, or mortality, or between statin administration and bacille Calmette-Guérin (BCG) immunotherapy effectiveness. A meta-analysis of 10 trials revealed a non-significant reduction of 11% in UBC risk among users compared with non-users in RCTs (RR: 0.89, 95% CI 0.68-1.16, p = 0.37) and a non-significant increase of 32% of UBC risk among statin users compared with non-users in the analysis of the cohort studies (RR: 1.32, 95% CI 0.76-2.30, p = 0.33). CONCLUSIONS Our results provide strong evidence to support the neutral effect of statins on UBC local control, recurrence, survival, and mortality, and on BCG immunotherapy. Our meta-analysis revealed a non-significant effect on UBC risk among statin users when compared with non-users, indicating no statin effect on UBC incidence and overall prognosis.
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Affiliation(s)
- Panagiotis Symvoulidis
- School of Medicine, European University Cyprus, Nicosia 2404, Cyprus; (P.S.); (C.T.); (C.Z.)
| | - Constantinos Tsioutis
- School of Medicine, European University Cyprus, Nicosia 2404, Cyprus; (P.S.); (C.T.); (C.Z.)
| | - Constantinos Zamboglou
- School of Medicine, European University Cyprus, Nicosia 2404, Cyprus; (P.S.); (C.T.); (C.Z.)
- Department of Radiation Oncology, Medical Center University of Freiburg, 79106 Freiburg, Germany
- Department of Internal Medicine, German Oncology Center, Limassol 4108, Cyprus
| | - Aris P. Agouridis
- School of Medicine, European University Cyprus, Nicosia 2404, Cyprus; (P.S.); (C.T.); (C.Z.)
- Department of Internal Medicine, German Oncology Center, Limassol 4108, Cyprus
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10
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Bladder Cancer and Risk Factors: Data from a Multi-Institutional Long-Term Analysis on Cardiovascular Disease and Cancer Incidence. J Pers Med 2023; 13:jpm13030512. [PMID: 36983694 PMCID: PMC10056598 DOI: 10.3390/jpm13030512] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Revised: 03/03/2023] [Accepted: 03/11/2023] [Indexed: 03/14/2023] Open
Abstract
Background: Bladder cancer (BCa) is a heterogeneous disease with a variable prognosis and natural history. Cardiovascular disease (CVD), although completely different, has several similarities and possible interactions with cancer. The association between them is still unknown, but common risk factors between the two suggest a shared biology. Materials and Methods: This was a retrospective study that included patients who underwent transurethral resection of bladder tumor at two high-volume institutions. Depending on the presence of a previous history of CVD or not, patients were divided into two groups. Results: A total of 2050 patients were included, and 1638 (81.3%) were diagnosed with bladder cancer. Regarding comorbidities, the most common were hypertension (59.9%), cardiovascular disease (23.4%) and diabetes (22.4%). At univariate analysis, independent risk factors for bladder cancer were age and male sex, while protective factors were cessation of smoking and presence of CVD. All these results, except for ex-smoker status, were confirmed at the multivariate analysis. Another analysis was performed for patients with high-risk bladder cancer and, in this case, the role of CVD was not statistically significant. Conclusions: Our study pointed out a positive association between CVD and BCa incidence; CVD was an independent protective factor for BCa. This effect was not confirmed for high-risk tumors. Several biological and genomics mechanisms clearly contribute to the onset of both diseases, suggesting a possible shared disease pathway and highlighting the complex interplay of cancer and CVD. CVD treatment can involve different drugs with a possible effect on cancer incidence, but, to date, findings are still inconclusive.
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11
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Xia L, Ding S, Wang X, Zhang X, Zhu L, Zhang H, Li H. Advances in ovarian cancer treatment using a combination of statins with other drugs. Front Pharmacol 2023; 13:1048484. [PMID: 36686716 PMCID: PMC9845598 DOI: 10.3389/fphar.2022.1048484] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Accepted: 12/14/2022] [Indexed: 01/06/2023] Open
Abstract
New anti-cancer drugs are constantly being developed, especially targeted drugs. Although these drugs have achieved significant clinical efficacy, they do not play a significant role in ovarian cancer. Moreover, the research cycle and costs of such drugs are often huge. The repositioning of conventional drugs has gradually become a concern. Statins, as traditional lipid-lowering drugs, play a role mainly by inhibiting HMGCR. In recent years, epidemiological studies and in vitro experiments have confirmed its anti-cancer effect, especially the effect of anti-ovarian cancer. The mutation rate of TP53 in ovarian cancer is as high as 95%, while HMGCR is often highly expressed in TP53 mutant tumors. However, the effect of prospective clinical trials is not ideal. This result seems understandable considering that it seems unrealistic for a lipid-lowering drug to completely inhibit tumor growth. Therefore, statins play more synergistic roles in the treatment of ovarian cancer. Because ovarian cancer is a highly heterogeneous tumor, it may be a good choice to deeply understand the mechanism of statins in the treatment of ovarian cancer and achieve precise treatment by combining it with other drugs.
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Affiliation(s)
- Lei Xia
- Department of Pathology, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Shichao Ding
- Department of Internal Medicine, The Third Affiliated Hospital of Shandong First Medical University, Jinan, China
| | - Xuezhen Wang
- School of Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Xiaoyu Zhang
- School of Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Lin Zhu
- School of Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Hairong Zhang
- Department of Obstetrics and Gynecology, Shandong Provincial Third Hospital, Jinan, China,*Correspondence: Hairong Zhang, ; Huirong Li,
| | - Huirong Li
- Department of Obstetrics and Gynecology, Shandong Provincial Third Hospital, Jinan, China,*Correspondence: Hairong Zhang, ; Huirong Li,
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12
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Su CH, Islam MM, Jia G, Wu CC. Statins and the Risk of Gastric Cancer: A Systematic Review and Meta-Analysis. J Clin Med 2022; 11:jcm11237180. [PMID: 36498753 PMCID: PMC9739712 DOI: 10.3390/jcm11237180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Revised: 11/25/2022] [Accepted: 11/30/2022] [Indexed: 12/12/2022] Open
Abstract
Previous epidemiological studies have reported that the use of statins is associated with a decreased risk of gastric cancer, although the beneficial effects of statins on the reduction of gastric cancer remain unclear. Therefore, we conducted a systematic review and meta-analysis to investigate the association between the use of statins and the risk of gastric cancer. Electronic databases such as PubMed, EMBASE, Scopus, and Web of Science were searched between 1 January 2000 and 31 August 2022. Two authors used predefined selection criteria to independently screen all titles, abstracts, and potential full texts. Observational studies (cohort and case-control) or randomized control trials that assessed the association between statins and gastric cancer were included in the primary and secondary analyses. The pooled effect sizes were calculated using the random-effects model. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines were followed to conduct this study. The total sample size across the 20 included studies was 11,870,553. The use of statins was associated with a reduced risk of gastric cancer (RRadjusted: 0.72; 95%CI: 0.64−0.81, p < 0.001). However, the effect size of statin use on the risk of gastric cancer was lower in Asian studies compared to Western studies (RRAsian: 0.62; 95%CI: 0.53−0.73 vs. RRwestern: 0.88; 95%CI: 0.79−0.99). These findings suggest that the use of statins is associated with a reduced risk of gastric cancer. This reverse association was even stronger among Asian people than Western individuals.
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Affiliation(s)
- Chun-Hsien Su
- Department of Exercise and Health Promotion, College of Kinesiology and Health, Chinese Culture University, Taipei 111396, Taiwan
- Graduate Institute of Sports Coaching Science, College of Kinesiology and Health, Chinese Culture University, Taipei 111396, Taiwan
| | - Md. Mohaimenul Islam
- International Center for Health Information Technology (ICHIT), Taipei Medical University, Taipei 111396, Taiwan
| | - Guhua Jia
- Sports Teaching Department, Shanghai University of Medicine & Health Sciences, Shanghai 201318, China
| | - Chieh-Chen Wu
- Department of Exercise and Health Promotion, College of Kinesiology and Health, Chinese Culture University, Taipei 111396, Taiwan
- Correspondence:
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13
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Lou D, Fu R, Gu L, Su H, Guan L. Association between statins exposure with incidence and prognosis of gastric cancer: an updated meta-analysis. Expert Rev Clin Pharmacol 2022; 15:1127-1138. [PMID: 35947078 DOI: 10.1080/17512433.2022.2112178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
BACKGROUND AND AIMS Previous research has revealed the role of statins in cancer prevention and treatment. This study aimed to determine the relationship between statins exposure and the incidence and prognosis of gastric cancer (GC). METHODS Relevant articles until January 2022 were systematically searched in PubMed, EBSCO, Web of Science, and Cochrane Library databases for comparison in GC with or without statins exposure. The primary referred outcomes were the occurrence of GC and the survival rate. A total of 19 articles were included in this meta-analysis. RESULTS The analysis showed that statins were associated with reduced GC incidence and increased GC survival rate. Subgroup analysis suggested a decreased incidence of GC in both Eastern and Western countries exposed to statins. Furthermore, the risk of GC was reduced in those exposed to lipophilic statins, yet not in those exposed to hydrophilic statins. CONCLUSIONS Statins were found to help lower the incidence and improve the survival rate of GC. Furthermore, the incidence of GC was influenced by the population's origin region and the type of statins used.
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Affiliation(s)
- Dandi Lou
- The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Rongrong Fu
- The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Lihu Gu
- Department of General Surgery, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang, China
| | - Hui Su
- Department of General Surgery, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang, China
| | - Like Guan
- Department of General Surgery, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang, China
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14
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Khazaaleh S, Sarmini MT, Alomari M, Al Momani L, El Kurdi B, Asfari M, Almomani Z, Romero-Marrero C. Statin Use Reduces the Risk of Hepatocellular Carcinoma: An Updated Meta-Analysis and Systematic Review. Cureus 2022; 14:e27032. [PMID: 35989795 PMCID: PMC9388192 DOI: 10.7759/cureus.27032] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/21/2022] [Indexed: 11/05/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver resulting in approximately 800,000 deaths annually. A growing body of research investigating statin use and HCC risk has shown conflicting results. We aim to evaluate the current evidence of statin impact on HCC risk. We performed a comprehensive literature search in PubMed, PubMed Central, Embase, and ScienceDirect databases from inception through May 2019 to identify all studies that evaluated the association between statin use and HCC. We included studies that presented an odds ratio (OR) with a 95% confidence interval (CI) or presented data sufficient to calculate the OR with a 95% CI. Statistical analysis was performed using the Comprehensive Meta-Analysis (CMA), Version 3 software, and a Forrest plot was generated. We assessed for publication bias using conventional techniques. Twenty studies (three randomized controlled trials, six cohorts, and 11 case-controls) with 2,668,497 patients including 24,341 cases of HCC were included in the meta-analysis. Our findings indicate a significant risk reduction of HCC among all statin users with a pooled odds ratio of 0.573 (95% CI: 0.491-0.668, I2= 86.57%) compared to non-users. No publication bias was found using Egger’s regression test or on visual inspection of the generated Funnel plot. The results indicate that statin use was associated with a 43% lower risk of HCC compared to statin non-users. Further prospective randomized research is needed to confirm the association.
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15
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Cheung KS, Yeung YWM, Wong WS, Li B, Seto WK, Leung WK. Statins associate with lower risk of biliary tract cancers: A systematic review and meta-analysis. Cancer Med 2022; 12:557-568. [PMID: 35698295 PMCID: PMC9844660 DOI: 10.1002/cam4.4942] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 05/02/2022] [Accepted: 05/28/2022] [Indexed: 01/26/2023] Open
Abstract
BACKGROUND Biliary tract cancers (BTCs), encompassing cholangiocarcinoma (CCA), gallbladder (GBC), and ampulla of Vater cancers (AVC), are common hepatobiliary cancer after hepatocellular carcinoma with a high mortality rate. As there is no effective chemopreventive agent to prevent BTCs, this study aimed to explore the role of statins on the risk of BTCs. METHODS PubMed, Embase, and Cochrane Library from inception until 24 April 2020 were searched according to the Meta-Analyses of Observational Studies in Epidemiology (MOOSE) guidelines. The adjusted risk ratios (aRRs) of BTCs and individual cancer were pooled using a random-effects model. RESULTS Eight observational studies (3 cohort and 5 case-control studies) were included with 10,485,231 patients. The median age was 68.0 years (IQR: 67.0-71.5) and 48.3% were male. Statins were associated with a lower risk of all BTCs (aRR: 0.67; 95% CI: 0.51-0.87). The pooled aRR for CCA was 0.60 (95% CI: 0.38-0.94) and GBC was 0.78 (95% CI: 0.68-0.90). There was only one study on AVC with aRR of 0.96 (95% CI: 0.66-1.41). The pooled aRR for lipophilic and hydrophilic statins was 0.78 (95% CI: 0.69-0.88) and 0.70 (95% CI: 0.61-0.80), respectively. The effects were attenuated in studies that adjusted for aspirin and/or non-steroidal anti-inflammatory drugs (aRR: 0.80, 95% CI: 0.72-0.89) and metformin (aRR: 0.80, 95% CI: 0.72-0.90). CONCLUSIONS Statins, both lipophilic and hydrophobic, were associated with a lower risk of BTCs, particularly CCA and GBC.
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Affiliation(s)
- Ka Shing Cheung
- Department of Medicine, The University of Hong KongQueen Mary HospitalHong Kong,Department of MedicineThe University of Hong Kong‐Shenzhen HospitalShenzhenChina
| | | | - Wing Sum Wong
- Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong
| | - Bofei Li
- Department of Thoracic Surgery, Shanghai Chest HospitalShanghai Jiao Tong UniversityChina
| | - Wai Kay Seto
- Department of Medicine, The University of Hong KongQueen Mary HospitalHong Kong,Department of MedicineThe University of Hong Kong‐Shenzhen HospitalShenzhenChina
| | - Wai K. Leung
- Department of Medicine, The University of Hong KongQueen Mary HospitalHong Kong
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16
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Wang Y, Wang W, Wang M, Shi J, Jia X, Dang S. A Meta-Analysis of Statin Use and Risk of Hepatocellular Carcinoma. Can J Gastroenterol Hepatol 2022; 2022:5389044. [PMID: 35356132 PMCID: PMC8958112 DOI: 10.1155/2022/5389044] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Revised: 02/25/2022] [Accepted: 02/26/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND The use of statins is a potential protective factor against the development of hepatocellular carcinoma. Therefore, we conducted a meta-analysis to evaluate the contribution of statins to the risk of hepatocellular carcinoma. METHODS We searched for PubMed and EMBASE through January 2021. RESULTS Thirty-two studies (eighteen cohort, eleven case-control, and three randomized controlled trials) reporting 56,838 cases of hepatocellular carcinoma in 4,963,518 persons were included. Statin users were less likely to develop hepatocellular carcinoma than nonusers (adjusted odds ratio, 0.58; 95% CI: 0.51-0.67). Stratified analysis showed that statins reduced the risk of hepatocellular carcinoma in Asian and Western populations (odds ratio, 0.54 vs. 0.60). Besides, statins have protective effects against hepatocellular carcinoma after hepatitis B virus (odds ratio, 0.44; 95% CI: 0.22-0.85) and hepatitis C virus infections (odds ratio, 0.53; 95% CI: 0.49-0.57). Statins have protective effects on people with chronic liver disease (odds ratio, 0.52; 95% CI: 0.40-0.68) and on the general population (odds ratio, 0.60; 95% CI: 0.50-0.72). Lipophilic statins can prevent hepatocellular carcinoma (odds ratio, 0.51, 95% CI: 0.46-0.57), while hydrophilic statins cannot (odds ratio, 0.77, 95% CI: 0.58-1.02). The single-drug analyses showed that simvastatin (odds ratio, 0.53, 95% CI: 0.48-0.59), atorvastatin (odds ratio, 0.54, 95% CI: 0.45-0.64), rosuvastatin (odds ratio, 0.55, 95% CI: 0.37-0.83), lovastatin (odds ratio, 0.30, 95% CI: 0.15-0.62), and pitavastatin (odds ratio, 0.36, 95% CI: 0.17-0.75) had significant benefits. Further studies have shown that those in the high-dose group experienced better effects in preventing hepatocellular carcinoma (adjusted hazard ratio, 0.38 vs. 0.55). Further research found that the combined use of aspirin did not increase the chemoprevention effect of liver cancer (odds ratio, 0.57; 95% CI: 0.40-0.81). In addition, the preventive effect of statins improved with the extension of follow-up time (odds ratio, 0.54 vs. 0.65). CONCLUSION Our meta-analysis shows that the use of statins is associated with a lower risk of liver cancer.
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Affiliation(s)
- Yikai Wang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China
| | - Wenjun Wang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China
| | - Muqi Wang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China
| | - Juanjuan Shi
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China
| | - Xiaoli Jia
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China
| | - Shuangsuo Dang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China
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Mansouri A, Reiner Ž, Ruscica M, Tedeschi-Reiner E, Radbakhsh S, Bagheri Ekta M, Sahebkar A. Antioxidant Effects of Statins by Modulating Nrf2 and Nrf2/HO-1 Signaling in Different Diseases. J Clin Med 2022; 11:1313. [PMID: 35268403 PMCID: PMC8911353 DOI: 10.3390/jcm11051313] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Revised: 02/14/2022] [Accepted: 02/21/2022] [Indexed: 02/06/2023] Open
Abstract
Statins are competitive inhibitors of hydroxymethylglutaryl-CoA (HMG-CoA) reductase and have been used to treat elevated low-density lipoprotein cholesterol (LDL-C) for almost four decades. Antioxidant and anti-inflammatory properties which are independent of the lipid-lowering effects of statins, i.e., their pleiotropic effects, might be beneficial in the prevention or treatment of many diseases. This review discusses the antioxidant effects of statins achieved by modulating the nuclear factor erythroid 2 related factor 2/ heme oxygenase-1 (Nrf2/HO-1) pathway in different organs and diseases. Nrf2 and other proteins involved in the Nrf2/HO-1 signaling pathway have a crucial role in cellular responses to oxidative stress, which is a risk factor for ASCVD. Statins can significantly increase the DNA-binding activity of Nrf2 and induce the expression of its target genes, such as HO-1 and glutathione peroxidase) GPx, (thus protecting the cells against oxidative stress. Antioxidant and anti-inflammatory properties of statins, which are independent of their lipid-lowering effects, could be partly explained by the modulation of the Nrf2/HO-1 pathway.
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Affiliation(s)
- Atena Mansouri
- Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand 9717853577, Iran;
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad 9177948954, Iran
| | - Željko Reiner
- Department of Internal Medicine, School of Medicine, University Hospital Center Zagreb, University of Zagreb, 10000 Zagreb, Croatia;
| | - Massimiliano Ruscica
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20100 Milan, Italy;
| | - Eugenia Tedeschi-Reiner
- University Hospital Center Sestre Milosrdnice, University of Osijek, Vinogradska Cesta 29, 10000 Zagreb, Croatia;
| | - Shabnam Radbakhsh
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran;
- Department of Medical Biotechnology and Nanotechnology, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran
| | - Mariam Bagheri Ekta
- Laboratory of Cellular and Molecular Pathology of Cardiovascular System, A.P. Avtsyn Research Institute of Human Morphology, 3 Tsyurupy Str., 117418 Moscow, Russia;
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad 9177948954, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran
- Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 9177948954, Iran
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18
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Zhao G, Ji Y, Ye Q, Ye X, Wo G, Chen X, Shao X, Tang J. Effect of statins use on risk and prognosis of breast cancer: a meta-analysis. Anticancer Drugs 2022; 33:e507-e518. [PMID: 34407042 DOI: 10.1097/cad.0000000000001151] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
The findings regarding the association between statins use and breast cancer are inconsistent. Given the widely and long-term use of statins as first choice drug for dyslipidemia, we conducted this meta-analysis for better understanding the associations between statins use and the risk and prognosis of breast cancer. Articles regarding effect of statins use on risk, prognosis of breast cancer and published before January 2021 were searched in the following databases: Web of Science, PubMed, EMBASE, Medline and Google Scholar. Odds ratios (ORs)/relative risks (RRs) or hazard ratios (HRs) and their 95% confidence intervals (CIs) were computed to generate a pooled effect size and 95% CI. The meta-analysis showed no significant association between statins use and risk of breast cancer (OR/RR = 1.02; 95% CI, 0.97-1.08; I2 = 76.1%; P < 0.001). The meta-analysis showed that statins use was associated with lower breast cancer recurrence, all-cause mortality and disease-specific mortality (breast cancer recurrence: HR = 0.75; 95% CI, 0.67-0.84; I2 = 31.7%; P = 0.154; all-cause mortality: HR = 0.82; 95% CI, 0.77-0.89; I2 = 67.5%; P < 0.001; and disease-specific mortality: HR = 0.82; 95% CI, 0.72-0.93; I2 = 83.6%; P < 0.001). Overall, in this report we demonstrated that the use of statins can improve the prognosis of breast cancer patients including lower risks of breast cancer recurrence, all-cause and cancer-specific mortality, though statins therapy may not have an impact on reducing the risk of breast cancer.
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Affiliation(s)
- Guodong Zhao
- Nanjing University of Chinese Medicine, Nanjing
- Department of General Surgery and Department of Oncology, Lianshui County People's Hospital, Huaian, Jiangsu, China
| | - Yanjun Ji
- Department of General Surgery and Department of Oncology, Lianshui County People's Hospital, Huaian, Jiangsu, China
| | - Qing Ye
- Department of General Surgery and Department of Oncology, Lianshui County People's Hospital, Huaian, Jiangsu, China
| | - Xin Ye
- Department of General Surgery and Department of Oncology, Lianshui County People's Hospital, Huaian, Jiangsu, China
| | - Guanqun Wo
- Nanjing University of Chinese Medicine, Nanjing
| | - Xi Chen
- Nanjing University of Chinese Medicine, Nanjing
| | - Xinyi Shao
- Nanjing University of Chinese Medicine, Nanjing
| | - Jinhai Tang
- Nanjing University of Chinese Medicine, Nanjing
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Seo SI, Park CH, Kim TJ, Bang CS, Kim JY, Lee KJ, Kim J, Kim HH, You SC, Shin WG. Aspirin, metformin, and statin use on the risk of gastric cancer: A nationwide population-based cohort study in Korea with systematic review and meta-analysis. Cancer Med 2021; 11:1217-1231. [PMID: 34970858 PMCID: PMC8855895 DOI: 10.1002/cam4.4514] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Revised: 12/01/2021] [Accepted: 12/03/2021] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND/AIMS Although several chemopreventive drugs against gastric cancer have been proposed, their effects have not been fully evaluated. We examined the impacts of aspirin, metformin, and statin use on gastric cancer development in a population-based cohort in Korea. METHODS We analyzed the association between potential chemopreventive drugs-aspirin, metformin, and statin-and gastric cancer through the Observational Medical Outcomes Partnership Common Data Model-based Korean nationwide cohort. Use of aspirin, metformin, and statin was defined by ≥365 days of prescriptions for each drug in the general population. To summarize the current evidence, we further performed a systematic review and meta-analysis of the impact of aspirin, metformin, and statin on gastric cancer development. RESULTS After propensity score matching, 31,839, 6764, and 10,251 subjects were observed for medians of 4.7, 4.2, and 4.2 years for aspirin, metformin, and statin analysis, respectively. Use of aspirin or statin was associated with lower risks of gastric cancer compared to their non-use, respectively (hazard ratio [HR] [95% confidence interval [CI]]: aspirin, 0.72 [0.60-0.85], p < 0.01; statin, 0.67 [0.49-0.92], p = 0.01). However, no association was observed between metformin use and gastric cancer development (HR [95% CI]: 0.85 [0.59-1.23], p = 0.40). A subgroup of subjects with diabetes mellitus showed a lower risk of gastric cancer development with statin use. The meta-analysis showed the highest effect size of gastric cancer development for statin, followed by aspirin and metformin. CONCLUSIONS Statin and aspirin use were associated with significantly reduced risks of gastric cancer development, while the use of metformin was not associated with the gastric cancer risk. The protective effect of statin against gastric cancer was also significant in patients with diabetes mellitus.
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Affiliation(s)
- Seung In Seo
- Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea.,Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
| | - Chan Hyuk Park
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Tae Jun Kim
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Chang Seok Bang
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea.,Department of Internal Medicine, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Korea
| | - Jae Young Kim
- University Industry Foundation, Hallym University, Chuncheon, Korea
| | - Kyung Joo Lee
- University Industry Foundation, Hallym University, Chuncheon, Korea
| | - Jinseob Kim
- Department of Epidemiology, School of Public Health, Seoul National University, Seoul, Korea
| | - Hyon Hee Kim
- Department of Statistics and Information Science, Dongduk Women's University, Seoul, Korea
| | - Seng Chan You
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Woon Geon Shin
- Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea.,Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
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Wang J, Li X. Impact of statin use on the risk and prognosis of hepatocellular carcinoma: a meta-analysis. Eur J Gastroenterol Hepatol 2021; 33:1603-1609. [PMID: 33405428 DOI: 10.1097/meg.0000000000002040] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND Previous studies have demonstrated that statin use might be associated with a reduced risk of hepatocellular carcinoma (HCC). However, the value of statin on the prognosis still needs to be evaluated. Based on the above considerations, we conducted a meta-analysis regarding the value of statin on the prevention and prognosis of HCC. METHODS Articles regarding the impact of statin use on the risk, prognosis of HCC and published before October 2020 were searched in the five databases. We computed odds ratio (OR)/relative risk (RR) or hazard ratio (HR) and 95% confidence intervals (CIs) regarding the association between statin use and the risk or prognosis of HCC by using STATA 12.0 software. RESULTS Twenty-six studies (including 1772 463 participants) detected the association between statin use and risk of HCC. Additionally, seven studies (including 8925 statin users and 76 487 no-statin users) explored the association between statin use and mortality of HCC. The meta-analysis showed that statin use was associated with lower risk and all-cause mortality of HCC with random effects models (risk: OR/RR = 0.57, 95% CI 0.49-0.65, I2 = 86.0%, P < 0.0001; all-cause mortality: HR = 0.80, 95% CI 0.68-0.94, I2 = 77.6%, P < 0.0001). However, statin use was not associated with cancer-specific mortality of HCC with a random effects model (HR = 0.80, 95% CI 0.62-1.03, I2 = 73.9%, P = 0.002). CONCLUSION In conclusion, our results have demonstrated the salutary effect of statin on the prevention and prognosis of HCC.
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Affiliation(s)
- Jianfeng Wang
- Department of Gastroenterology, Baoshan Branch of Shanghai Renji Hospital, Shanghai, China
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21
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Pandey M, Cuddihy G, Gordon JA, Cox ME, Wasan KM. Inhibition of Scavenger Receptor Class B Type 1 (SR-B1) Expression and Activity as a Potential Novel Target to Disrupt Cholesterol Availability in Castration-Resistant Prostate Cancer. Pharmaceutics 2021; 13:1509. [PMID: 34575583 PMCID: PMC8467449 DOI: 10.3390/pharmaceutics13091509] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 09/04/2021] [Accepted: 09/08/2021] [Indexed: 02/07/2023] Open
Abstract
There have been several studies that have linked elevated scavenger receptor class b type 1 (SR-B1) expression and activity to the development and progression of castration-resistant prostate cancer (CRPC). SR-B1 facilitates the influx of cholesterol to the cell from lipoproteins in systemic circulation. This influx of cholesterol may be important for many cellular functions, including the synthesis of androgens. Castration-resistant prostate cancer tumors can synthesize androgens de novo to supplement the loss of exogenous sources often induced by androgen deprivation therapy. Silencing of SR-B1 may impact the ability of prostate cancer cells, particularly those of the castration-resistant state, to maintain the intracellular supply of androgens by removing a supply of cholesterol. SR-B1 expression is elevated in CRPC models and has been linked to poor survival of patients. The overarching belief has been that cholesterol modulation, through either synthesis or uptake inhibition, will impact essential signaling processes, impeding the proliferation of prostate cancer. The reduction in cellular cholesterol availability can impede prostate cancer proliferation through both decreased steroid synthesis and steroid-independent mechanisms, providing a potential therapeutic target for the treatment of prostate cancer. In this article, we discuss and highlight the work on SR-B1 as a potential novel drug target for CRPC management.
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Affiliation(s)
- Mitali Pandey
- Department of Urological Sciences, Faculty of Medicine, University of British Columbia, Vancouver Prostate Centre, Vancouver, BC V6T 1Z3, Canada; (M.P.); (M.E.C.)
| | - Grace Cuddihy
- College of Pharmacy and Nutrition, University of Saskatchewan, 104 Clinic Place, Saskatoon, SK S7N 2Z4, Canada;
| | - Jacob A. Gordon
- Oncology Bioscience, Oncology R&D, AstraZeneca, Boston, MA 02451, USA;
| | - Michael E. Cox
- Department of Urological Sciences, Faculty of Medicine, University of British Columbia, Vancouver Prostate Centre, Vancouver, BC V6T 1Z3, Canada; (M.P.); (M.E.C.)
| | - Kishor M. Wasan
- Department of Urological Sciences, Faculty of Medicine, University of British Columbia, Vancouver Prostate Centre, Vancouver, BC V6T 1Z3, Canada; (M.P.); (M.E.C.)
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22
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Wong YJ, Qiu TY, Ng GK, Zheng Q, Teo EK. Efficacy and Safety of Statin for Hepatocellular Carcinoma Prevention Among Chronic Liver Disease Patients: A Systematic Review and Meta-analysis. J Clin Gastroenterol 2021; 55:615-623. [PMID: 33606427 DOI: 10.1097/mcg.0000000000001478] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Accepted: 10/29/2020] [Indexed: 02/05/2023]
Abstract
INTRODUCTION AND AIM Hepatocellular carcinoma (HCC) is a deadly complication among patients with chronic liver disease (CLD). Controversies on the efficacy and safety of statin to prevent HCC among patients with CLD remain despite the growing evidences. We aim to investigate the efficacy and safety of using statin for HCC prevention among adult with CLD. METHODS We performed a systematic search of 4 electronic databases (PubMed/MEDLINE, EMBASE, Cochrane library, and ClinicalTrial.gov) up to April 15, 2020. We selected all types of studies evaluating the statin use and the risk of HCC among CLD patients, regardless of language, region, publication date, or status. The primary endpoint was the pooled risk of HCC. The secondary endpoint was the risk of statin-associated myopathy. RESULT From 583 citations, we included a total of 13 studies (1,742,260 subjects, 7 types of statins), fulfilling the inclusion criteria, evaluating efficacy and safety of statin in CLD patients for HCC prevention. All studies were observational (2 nested case-control studies, 11 cohort studies), and no randomised trial was identified. We found that statin user has a lower pooled risk of HCC development (hazard ratio=0.57, 95% confidence interval: 0.52-0.62, I2=42%). HCC reduction was consistent among statin users in cirrhosis, hepatitis B virus, and hepatitis C virus infections. The risk of statin-associated myopathy was similar between statin user and nonuser (hazard ratio=1.07, 95% confidence interval=0.91-1.27). CONCLUSION Statin use was safe and associated with a lower pooled risk of HCC development among adults with CLD. Given the bias with observation studies, prospective randomised trial is needed to confirm this finding.
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Affiliation(s)
- Yu-Jun Wong
- Department of Gastroenterology and Hepatology, Changi General Hospital
- Yong Loo Lin School of Medicine, National University of Singapore
| | - Tian-Yu Qiu
- Department of Gastroenterology and Hepatology, Changi General Hospital
| | | | | | - Eng Kiong Teo
- Department of Gastroenterology and Hepatology, Changi General Hospital
- Yong Loo Lin School of Medicine, National University of Singapore
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Marabotto E, Pellegatta G, Sheijani AD, Ziola S, Zentilin P, De Marzo MG, Giannini EG, Ghisa M, Barberio B, Scarpa M, Angriman I, Fassan M, Savarino V, Savarino E. Prevention Strategies for Esophageal Cancer-An Expert Review. Cancers (Basel) 2021; 13:2183. [PMID: 34062788 PMCID: PMC8125297 DOI: 10.3390/cancers13092183] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Revised: 04/27/2021] [Accepted: 04/28/2021] [Indexed: 02/06/2023] Open
Abstract
In the last 30 years, we have witnessed a rapid increase in the incidence and prevalence of esophageal cancer in many countries around the word. However, despite advancements in diagnostic technologies, the early detection of this cancer is rare, and its prognosis remains poor, with only about 20% of these patients surviving for 5 years. The two major forms are the esophageal squamous cell carcinoma (ESCC), which is particularly frequent in the so-called Asian belt, and the esophageal adenocarcinoma (EAC), which prevails in Western populations. This review provides a summary of the epidemiological features and risk factors associated with these tumors. Moreover, a major focus is posed on reporting and highlighting the various preventing strategies proposed by the most important international scientific societies, particularly in high-risk populations, with the final aim of detecting these lesions as early as possible and therefore favoring their definite cure. Indeed, we have conducted analysis with attention to the current primary, secondary and tertiary prevention guidelines in both ESCC and EAC, attempting to emphasize unresolved research and clinical problems related to these topics in order to improve our diagnostic strategies and management.
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Affiliation(s)
- Elisa Marabotto
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; (E.M.); (A.D.S.); (S.Z.); (P.Z.); (M.G.D.M.); (E.G.G.); (V.S.)
| | - Gaia Pellegatta
- Digestive Endoscopy Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, via Manzoni 56, 20089 Milan, Italy;
| | - Afscin Djahandideh Sheijani
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; (E.M.); (A.D.S.); (S.Z.); (P.Z.); (M.G.D.M.); (E.G.G.); (V.S.)
| | - Sebastiano Ziola
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; (E.M.); (A.D.S.); (S.Z.); (P.Z.); (M.G.D.M.); (E.G.G.); (V.S.)
| | - Patrizia Zentilin
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; (E.M.); (A.D.S.); (S.Z.); (P.Z.); (M.G.D.M.); (E.G.G.); (V.S.)
| | - Maria Giulia De Marzo
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; (E.M.); (A.D.S.); (S.Z.); (P.Z.); (M.G.D.M.); (E.G.G.); (V.S.)
| | - Edoardo Giovanni Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; (E.M.); (A.D.S.); (S.Z.); (P.Z.); (M.G.D.M.); (E.G.G.); (V.S.)
| | - Matteo Ghisa
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (M.G.); (B.B.)
| | - Brigida Barberio
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (M.G.); (B.B.)
| | - Marco Scarpa
- Clinica Chirurgica 1, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (M.S.); (I.A.)
| | - Imerio Angriman
- Clinica Chirurgica 1, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (M.S.); (I.A.)
| | - Matteo Fassan
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, 35121 Padua, Italy;
| | - Vincenzo Savarino
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; (E.M.); (A.D.S.); (S.Z.); (P.Z.); (M.G.D.M.); (E.G.G.); (V.S.)
| | - Edoardo Savarino
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (M.G.); (B.B.)
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Wang G, Liu X, Wang D, Sun M, Yang Q. Identification and Development of Subtypes With Poor Prognosis in Pan-Gynecological Cancer Based on Gene Expression in the Glycolysis-Cholesterol Synthesis Axis. Front Oncol 2021; 11:636565. [PMID: 33842342 PMCID: PMC8025671 DOI: 10.3389/fonc.2021.636565] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Accepted: 02/19/2021] [Indexed: 12/24/2022] Open
Abstract
Objective: Metabolic reprogramming is an important biomarker of cancer. Metabolic adaptation driven by oncogenes allows tumor cells to survive and grow in a complex tumor microenvironment. The heterogeneity of tumor metabolism is related to survival time, somatic cell-driven gene mutations, and tumor subtypes. Using the heterogeneity of different metabolic pathways for the classification of gynecological pan-cancer is of great significance for clinical decision-making and prognosis prediction. Methods: RNA sequencing data for patients with ovarian, cervical, and endometrial cancer were downloaded from The Cancer Genome Atlas database. Genes related to glycolysis and cholesterol were extracted and clustered coherently by using ConsensusClusterPlus. The mutations and copy number variations in different subtypes were compared, and the immune scores of the samples were evaluated. The limma R package was used to identify differentially expressed genes between subtypes, and the WebGestaltR package (V0.4.2) was used to conduct Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology functional enrichment analyses. A risk score model was constructed based on multivariate Cox analysis. Prognostic classification efficiency was analyzed by using timeROC, and internal and external cohorts were used to verify the robustness of the model. Results: Based on the expression of 11 glycolysis-related genes and seven cholesterol-related genes, 1,204 samples were divided into four metabolic subtypes (quiescent, glycolysis, cholesterol, and mixed). Immune infiltration scores showed significant differences among the four subtypes. Survival analysis showed that the prognosis of the cholesterol subtype was better than that of the quiescent subtype. A nine-gene signature was constructed based on differentially expressed genes between the cholesterol and quiescent subtypes, and it was validated by using an independent cohort of the International Cancer Genome Consortium. Compared with existing models, our nine-gene signature had good prediction performance. Conclusion: The metabolic classification of gynecological pan-cancer based on metabolic reprogramming may provide an important basis for clinicians to choose treatment options, predict treatment resistance, and predict patients' clinical outcomes.
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Affiliation(s)
- Guangwei Wang
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xiaofei Liu
- Department of Obstetrics and Gynecology, Shenyang Women's and Children's Hospital, Shenyang, China
| | - Dandan Wang
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Meige Sun
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Qing Yang
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
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Trivedi LU, Femnou Mbuntum L, Halm EA, Mansi I. Is Statin Use Associated With Risk of Thyroid Diseases? Results of a Retrospective Cohort Study. Ann Pharmacother 2021; 55:1110-1119. [PMID: 33412925 DOI: 10.1177/1060028020986552] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Given the ubiquity of statin use and prevalence of thyroid diseases, such as thyroid cancer, hyperthyroidism, and thyroiditis, understanding their association deserves further attention. OBJECTIVE To examine the association between statin use and thyroid cancer, thyrotoxicosis, goiter, and thyroiditis. METHODS Using Tricare data, 2 propensity score (PS)-matched cohorts of statin users and nonusers were formed: (1) a PS-matched general cohort (all patients aged 30-85 years) and (2) a PS-matched healthy cohort (excluded patients with cardiovascular diseases or severe comorbidities). Outcomes were thyroid cancer, thyrotoxicosis, goiter, and thyroiditis. Odds ratios (ORs) and 95% CIs of outcomes were estimated using conditional regression analysis. RESULTS Of 43 438 patients, the PS-matched general cohort matched 6342 statin users to 6342 nonusers. The OR of thyroid cancer was 0.62 (95% CI = 0.39-0.996). There was no significant difference between statin users and nonusers in risk of thyrotoxicosis (OR = 0.88; 95% CI = 0.71-1.09), goiter (OR = 0.9; 95% CI = 0.77-1.03), or thyroiditis (OR = 0.78; 95% CI = 0.53-1.15). In the PS-matched healthy cohort (3351 statin users to 3351 nonusers), there was no difference between statin users and nonusers in any outcome. Limitations of the study include its retrospective observational design and use of administrative codes in outcomes ascertainment. CONCLUSION AND RELEVANCE This study did not demonstrate any association of statins with harmful effects on thyroid diseases, which offers assurance to clinicians and patients. Furthermore, statin use appears to be associated with a decreased risk of thyroid cancer, but more studies are needed.
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Affiliation(s)
| | | | - Ethan A Halm
- University of Texas Southwestern, Dallas, TX, USA
| | - Ishak Mansi
- University of Texas Southwestern, Dallas, TX, USA.,VA North Texas Health System, Dallas, TX, USA
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Revilla G, Cedó L, Tondo M, Moral A, Pérez JI, Corcoy R, Lerma E, Fuste V, Reddy ST, Blanco-Vaca F, Mato E, Escolà-Gil JC. LDL, HDL and endocrine-related cancer: From pathogenic mechanisms to therapies. Semin Cancer Biol 2020; 73:134-157. [PMID: 33249202 DOI: 10.1016/j.semcancer.2020.11.012] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2020] [Revised: 10/19/2020] [Accepted: 11/16/2020] [Indexed: 02/07/2023]
Abstract
Cholesterol is essential for a variety of functions in endocrine-related cells, including hormone and steroid production. We have reviewed the progress to date in research on the role of the main cholesterol-containing lipoproteins; low-density lipoprotein (LDL) and high-density lipoprotein (HDL), and their impact on intracellular cholesterol homeostasis and carcinogenic pathways in endocrine-related cancers. Neither LDL-cholesterol (LDL-C) nor HDL-cholesterol (HDL-C) was consistently associated with endocrine-related cancer risk. However, preclinical studies showed that LDL receptor plays a critical role in endocrine-related tumor cells, mainly by enhancing circulating LDL-C uptake and modulating tumorigenic signaling pathways. Although scavenger receptor type BI-mediated uptake of HDL could enhance cell proliferation in breast, prostate, and ovarian cancer, these effects may be counteracted by the antioxidant and anti-inflammatory properties of HDL. Moreover, 27-hydroxycholesterol a metabolite of cholesterol promotes tumorigenic processes in breast and epithelial thyroid cancer. Furthermore, statins have been reported to reduce the incidence of breast, prostate, pancreatic, and ovarian cancer in large clinical trials, in part because of their ability to lower cholesterol synthesis. Overall, cholesterol homeostasis deregulation in endocrine-related cancers offers new therapeutic opportunities, but more mechanistic studies are needed to translate the preclinical findings into clinical therapies.
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Affiliation(s)
- Giovanna Revilla
- Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques (IIB) Sant Pau, C/ Sant Quintí 77, 08041 Barcelona Spain; Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, C/ Antoni M. Claret 167, 08025 Barcelona, Spain
| | - Lídia Cedó
- Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques (IIB) Sant Pau, C/ Sant Quintí 77, 08041 Barcelona Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), C/ Monforte de Lemos 3-5, 28029 Madrid, Spain
| | - Mireia Tondo
- Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques (IIB) Sant Pau, C/ Sant Quintí 77, 08041 Barcelona Spain; Servei de Bioquímica, Hospital de la Santa Creu i Sant Pau, C/ Sant Quintí 89, 08041 Barcelona, Spain
| | - Antonio Moral
- Department of General Surgery, Hospital de la Santa Creu i Sant Pau, C/ Sant Quintí 89, 08041 Barcelona, Spain; Departament de Medicina, Universitat Autònoma de Barcelona, C/ Antoni M. Claret 167, 08025 Barcelona, Spain
| | - José Ignacio Pérez
- Department of General Surgery, Hospital de la Santa Creu i Sant Pau, C/ Sant Quintí 89, 08041 Barcelona, Spain
| | - Rosa Corcoy
- Departament de Medicina, Universitat Autònoma de Barcelona, C/ Antoni M. Claret 167, 08025 Barcelona, Spain; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), C/ Monforte de Lemos 3-5, 28029 Madrid, Spain; Department of Endocrinology and Nutrition, Hospital de la Santa Creu i Sant Pau, C/ Sant Quintí 89, 08041 Barcelona, Spain
| | - Enrique Lerma
- Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques (IIB) Sant Pau, C/ Sant Quintí 77, 08041 Barcelona Spain; Department of Anatomic Pathology, Hospital de la Santa Creu i Sant Pau, C/ Sant Quintí 89, 08041 Barcelona, Spain
| | - Victoria Fuste
- Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques (IIB) Sant Pau, C/ Sant Quintí 77, 08041 Barcelona Spain; Department of Anatomic Pathology, Hospital de la Santa Creu i Sant Pau, C/ Sant Quintí 89, 08041 Barcelona, Spain
| | - Srivinasa T Reddy
- Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095-1736, USA
| | - Francisco Blanco-Vaca
- Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques (IIB) Sant Pau, C/ Sant Quintí 77, 08041 Barcelona Spain; Servei de Bioquímica, Hospital de la Santa Creu i Sant Pau, C/ Sant Quintí 89, 08041 Barcelona, Spain.
| | - Eugènia Mato
- Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques (IIB) Sant Pau, C/ Sant Quintí 77, 08041 Barcelona Spain; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), C/ Monforte de Lemos 3-5, 28029 Madrid, Spain.
| | - Joan Carles Escolà-Gil
- Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques (IIB) Sant Pau, C/ Sant Quintí 77, 08041 Barcelona Spain.
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MOHAMMADIAN-HAFSHEJANI ABDOLLAH, SHERWIN CATHERINEM, HEIDARI-SOURESHJANI SAEID. Do statins play any role in reducing the incidence and mortality of ovarian cancer? A systematic review and meta-analysis. JOURNAL OF PREVENTIVE MEDICINE AND HYGIENE 2020; 61:E331-E339. [PMID: 33150223 PMCID: PMC7595068 DOI: 10.15167/2421-4248/jpmh2020.61.3.1497] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Accepted: 05/18/2020] [Indexed: 01/15/2023]
Abstract
Introduction This systematic review and meta-analysis aimed to investigate the relationship between statin consumption and risk of incidence of ovarian cancer (OC) and associated mortality. Methods Computerized searches were conducted in three electronic databases (PubMed, Web of Science, and Scopus). Two calibrated authors performed the publications selection, data extraction, and quality assessment of the selected publications. The quality of the included articles was evaluated using the Newcastle-Ottawa Scale (NOS) for observational studies, and Jadad criteria for randomized clinical trials (RCTs). The electronic searches retrieved 2272 titles/abstracts. After the deletion of duplicate publications, 2030 titles/abstracts were assessed. Eighteen articles were included. Results Meta-analysis demonstrated that risk ratio (RR) of the association between statin consumption and OC incidence was 0.88 (95% CI = 0.75-1.03, P = 0.109). Patients receiving statin were less likely to die than those who did not receive statin, with a statistically significant association [RR = 0.76 (95% CI 0.67-0.86, P = 0.0001)]. There was no evidence of publication bias in examining the association between statin consumption and the risk of incidence and mortality from OC. Conclusions This study determined that statin use reduced the incidence risk of OC and significantly increased the survival in OC patients.
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Affiliation(s)
- ABDOLLAH MOHAMMADIAN-HAFSHEJANI
- Department of Epidemiology and Biostatistics, School of Public Health, Shahrekord University of Medical Sciences, Shahrekord, Iran
- Pediatric Clinical Pharmacology, Department of Pediatrics, Wright State University Boonshoft School of Medicine, Dayton Children’s Hospital, One Children’s Plaza, Dayton, Ohio, USA
| | - CATHERINE M.T. SHERWIN
- Pediatric Clinical Pharmacology, Department of Pediatrics, Wright State University Boonshoft School of Medicine, Dayton Children’s Hospital, One Children’s Plaza, Dayton, Ohio, USA
| | - SAEID HEIDARI-SOURESHJANI
- Shahrekord University of Medical Sciences, Shahrekord, Iran
- Correspondence: Saeid Heidari-Soureshjani, Circuit of Research and Technology, Shahrekord University of Medical Sciences, Shahrekord, Iran - Tel. +98 9131833509 - Fax: +98 383351031 - E-mail:
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Irvin S, Clarke MA, Trabert B, Wentzensen N. Systematic review and meta-analysis of studies assessing the relationship between statin use and risk of ovarian cancer. Cancer Causes Control 2020; 31:869-879. [PMID: 32685996 DOI: 10.1007/s10552-020-01327-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Accepted: 07/07/2020] [Indexed: 12/24/2022]
Abstract
PURPOSE The link between lipid-stabilizing medications and epithelial ovarian carcinogenesis is incompletely understood. Statins may reduce ovarian cancer risk, but results are inconclusive. METHODS We conducted a systematic review and meta-analysis of studies reporting associations between statin use and ovarian cancer risk in PubMed. Summary risk ratios (RRs) and confidence intervals (CIs) were calculated. Subgroup analyses by cancer histotype, statin class (lipo- or hydrophilic) and duration of statin use were conducted. Use of individual statins in populations was assessed to determine population-specific differences in statin types. RESULTS Nine studies with 435,237 total women were included (1 randomized controlled trial (RCT); 4 prospective; 4 case-control). Statin use was associated with a reduced risk of ovarian cancer (RR 0.87, 95% CI 0.74-1.03) and risk was significantly reduced in populations with low pravastatin use (RR 0.83, 95% CI 0.70-0.99). Risk estimates varied by statin class (3 studies; lipophilic: RR 0.88, 95% CI 0.69-1.12; hydrophilic: RR 1.06, 95% CI 0.72-1.57) and cancer histotype (3 studies; serous: RR 0.95, 95% CI 0.69-1.30; clear cell: RR 1.17, 95% CI 0.74-1.86). Long-term use was associated with a reduced risk of ovarian cancer (RR 0.77, 95% CI 0.54-1.10) that further reduced when pravastatin use was low (RR 0.68, 95% CI 0.46-1.01). Between-study heterogeneity was high overall and in subgroups (I2 > 60%). CONCLUSION Statins may be associated with a reduced risk of ovarian cancer, but the effect likely differs by individual statin, duration of use and cancer histotype. Additional well-powered studies are needed to elucidate important subgroup effects.
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Affiliation(s)
- Sarah Irvin
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD, 20850, USA.
| | - Megan A Clarke
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD, 20850, USA
| | - Britton Trabert
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD, 20850, USA
| | - Nicolas Wentzensen
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD, 20850, USA
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Statin use and the risk of multiple myeloma: a PRISMA-compliant meta-analysis. Ann Hematol 2020; 99:1805-1812. [PMID: 32613280 DOI: 10.1007/s00277-020-04157-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Accepted: 06/18/2020] [Indexed: 10/23/2022]
Abstract
Previous studies exploring associations between statin use and risk of multiple myeloma (MM) showed inconsistent results. We searched for articles published in English in databases (PubMed, Web of Science, EMBASE, Medline, and Google Scholar) before October 2019. The multivariate odds ratio (OR)/relative risk (RR) and 95% confidence intervals (CI) were computed to explore associations between statin use and risk of MM. The study indicated that statin users showed significantly lower risks of MM with a random effects model (OR/RR = 0.77, 95% CI 0.63 to 0.95, I2 = 63.1%, p for Q test = 0.001). Subgroup analyses showed that statin users showed significantly lower risks of MM in Caucasian populations with a fixed effects model (OR/RR = 0.72, 95% CI 0.59 to 0.88, I2 = 43.5%, p for Q test = 0.060), whereas no significant association was shown between statin use and risks of MM in Asian populations with a random effects model. Additionally, Subgroup analyses showed that statin users showed significantly lower risks of MM in cohort studies with a fixed effects model (RR = 0.83, 95% CI 0.74 to 0.93, I2 = 0.0%, p for Q test = 0.429), whereas no significant association was shown between statin use and risks of MM in case-control studies with a random effects model. In conclusion, the present study indicated that statin use might be a protective factor for MM incidence. However, the relationship between statin use and MM risk requires repeated and large prospective studies to be verified.
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Alexandrova E, Pecoraro G, Sellitto A, Melone V, Ferravante C, Rocco T, Guacci A, Giurato G, Nassa G, Rizzo F, Weisz A, Tarallo R. An Overview of Candidate Therapeutic Target Genes in Ovarian Cancer. Cancers (Basel) 2020; 12:cancers12061470. [PMID: 32512900 PMCID: PMC7352306 DOI: 10.3390/cancers12061470] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 05/31/2020] [Accepted: 06/02/2020] [Indexed: 12/25/2022] Open
Abstract
Ovarian cancer (OC) shows the highest mortality rate among gynecological malignancies and, because of the absence of specific symptoms, it is frequently diagnosed at an advanced stage, mainly due to the lack of specific and early biomarkers, such as those based on cancer molecular signature identification. Indeed, although significant progress has been made toward improving the clinical outcome of other cancers, rates of mortality for OC are essentially unchanged since 1980, suggesting the need of new approaches to identify and characterize the molecular mechanisms underlying pathogenesis and progression of these malignancies. In addition, due to the low response rate and the high frequency of resistance to current treatments, emerging therapeutic strategies against OC focus on targeting single factors and pathways specifically involved in tumor growth and metastasis. To date, loss-of-function screenings are extensively applied to identify key drug targets in cancer, seeking for more effective, disease-tailored treatments to overcome lack of response or resistance to current therapies. We review here the information relative to essential genes and functional pathways recently discovered in OC, often strictly interconnected with each other and representing promising biomarkers and molecular targets to treat these malignancies.
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Affiliation(s)
- Elena Alexandrova
- Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitan”, University of Salerno, 84081 Baronissi, Italy; (E.A.); (G.P.); (A.S.); (V.M.); (C.F.); (T.R.); (G.G.); (G.N.); (F.R.)
| | - Giovanni Pecoraro
- Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitan”, University of Salerno, 84081 Baronissi, Italy; (E.A.); (G.P.); (A.S.); (V.M.); (C.F.); (T.R.); (G.G.); (G.N.); (F.R.)
| | - Assunta Sellitto
- Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitan”, University of Salerno, 84081 Baronissi, Italy; (E.A.); (G.P.); (A.S.); (V.M.); (C.F.); (T.R.); (G.G.); (G.N.); (F.R.)
| | - Viola Melone
- Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitan”, University of Salerno, 84081 Baronissi, Italy; (E.A.); (G.P.); (A.S.); (V.M.); (C.F.); (T.R.); (G.G.); (G.N.); (F.R.)
| | - Carlo Ferravante
- Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitan”, University of Salerno, 84081 Baronissi, Italy; (E.A.); (G.P.); (A.S.); (V.M.); (C.F.); (T.R.); (G.G.); (G.N.); (F.R.)
- Genomix4Life, via S. Allende 43/L, 84081 Baronissi, Italy;
| | - Teresa Rocco
- Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitan”, University of Salerno, 84081 Baronissi, Italy; (E.A.); (G.P.); (A.S.); (V.M.); (C.F.); (T.R.); (G.G.); (G.N.); (F.R.)
- Genomix4Life, via S. Allende 43/L, 84081 Baronissi, Italy;
| | - Anna Guacci
- Genomix4Life, via S. Allende 43/L, 84081 Baronissi, Italy;
| | - Giorgio Giurato
- Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitan”, University of Salerno, 84081 Baronissi, Italy; (E.A.); (G.P.); (A.S.); (V.M.); (C.F.); (T.R.); (G.G.); (G.N.); (F.R.)
| | - Giovanni Nassa
- Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitan”, University of Salerno, 84081 Baronissi, Italy; (E.A.); (G.P.); (A.S.); (V.M.); (C.F.); (T.R.); (G.G.); (G.N.); (F.R.)
| | - Francesca Rizzo
- Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitan”, University of Salerno, 84081 Baronissi, Italy; (E.A.); (G.P.); (A.S.); (V.M.); (C.F.); (T.R.); (G.G.); (G.N.); (F.R.)
| | - Alessandro Weisz
- Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitan”, University of Salerno, 84081 Baronissi, Italy; (E.A.); (G.P.); (A.S.); (V.M.); (C.F.); (T.R.); (G.G.); (G.N.); (F.R.)
- CRGS-Genome Research Center for Health, University of Salerno Campus of Medicine, 84081 Baronissi, Italy
- Correspondence: (A.W.); (R.T.); Tel.: +39-089-965043 (A.W.); +39-089-965067 (R.T.)
| | - Roberta Tarallo
- Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitan”, University of Salerno, 84081 Baronissi, Italy; (E.A.); (G.P.); (A.S.); (V.M.); (C.F.); (T.R.); (G.G.); (G.N.); (F.R.)
- Correspondence: (A.W.); (R.T.); Tel.: +39-089-965043 (A.W.); +39-089-965067 (R.T.)
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Statin Use and the Risk of Hepatocellular Carcinoma: A Meta-Analysis of Observational Studies. Cancers (Basel) 2020; 12:cancers12030671. [PMID: 32183029 PMCID: PMC7139959 DOI: 10.3390/cancers12030671] [Citation(s) in RCA: 68] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Revised: 02/24/2020] [Accepted: 03/11/2020] [Indexed: 01/27/2023] Open
Abstract
Background and Aims: Statins are the first-line medication to treating hypercholesterolemia. Several studies have investigated the impact of statins on the risk of hepatocellular carcinoma (HCC). However, the extent to which statins may prevent HCC remains uncertain. Therefore, we performed a meta-analysis of relevant studies to quantify the magnitude of the association between statins use and the risk of HCC. Methods: A systematic literature search of PubMed, EMBASE, Google Scholar, Web of Science, and Scopus was performed for studies published between January 1, 1990, and September 1, 2019, with no restriction of language. Two reviewers independently evaluated the literature and included observational and experimental studies that reported the association between statin use and HCC risk. The random-effect model was used to calculate the overall risk ratio (RR) with a 95% confidence interval (CI), and the heterogeneity among the studies was assessed using the Q statistic and I2 statistic. The Newcastle Ottawa Scale (NOS) was also used to evaluate the quality of the included studies. Results: A total of 24 studies with 59,073 HCC patients was identified. Statin use was associated with a reduced risk of HCC development (RR: 0.54, 95% CI: 0.47–0.61, I2 = 84.39%) compared with nonusers. Moreover, the rate of HCC reduction was also significant among patients with diabetes (RR: 0.44, 95% CI: 0.28–0.70), liver cirrhosis (RR: 0.36, 95% CI: 0.30–0.42), and antiviral therapy (RR: 0.21, 95% CI: 0.08–0.59) compared with nonusers. Conclusion: This study serves as additional evidence supporting the beneficial inhibitory effect of statins on HCC incidence. The subgroup analyses of this study also highlight that statins are significantly associated with a reduced risk of HCC and may help to direct future prevention efforts. Additional large clinical studies are needed to determine whether statins are associated with a lower risk of HCC.
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Ponvilawan B, Charoenngam N, Rittiphairoj T, Ungprasert P. Receipt of Statins Is Associated With Lower Risk of Multiple Myeloma: Systematic Review and Meta-analysis. CLINICAL LYMPHOMA MYELOMA & LEUKEMIA 2020; 20:e399-e413. [PMID: 32199765 DOI: 10.1016/j.clml.2020.02.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/03/2019] [Revised: 01/26/2020] [Accepted: 02/13/2020] [Indexed: 01/06/2023]
Abstract
BACKGROUND Studies on receipt of statins and risk of multiple myeloma (MM) yielded conflicting results. This systematic review and meta-analysis was conducted in order to comprehensively investigate the relationship between receipt of statins and risk of MM. PATIENTS AND METHODS Potentially eligible studies that compared the risk of MM between statin recipients and those who did not receive statins were identified from Medline and Embase databases from inception to August 2019 using a search strategy that comprised terms for "statin" and "multiple myeloma." To be eligible, cohort studies must have recruited 2 groups of participants, statin recipients and nonrecipients, and followed their participants for incident MM. Eligible case-control studies must have recruited cases of MM and controls without MM, and must have explored the history of receipt of statins. Relative risk, hazard risk ratio, standardized incidence ratio, or odds ratio (OR) of this association must be reported. Relative risk and standard error from each study were extracted and combined using random-effect generic inverse variance. Relative risk of cohort study was used as an estimate for OR to calculate the pooled effect estimate along with the OR of the case-control studies. RESULTS A total of 1744 articles were identified using the search strategy, and 10 studies were included in the meta-analysis. The odds of MM were significantly lower among statin recipients than nonrecipients, with a pooled OR of 0.80 (95% confidence interval, 0.68-0.93; I2 72%). The funnel plot was relatively symmetrical and did not suggest publication bias. CONCLUSION Receipt of statins is associated with a significant 20% reduction in the odds of MM.
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Affiliation(s)
- Ben Ponvilawan
- Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
| | - Nipith Charoenngam
- Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | | | - Patompong Ungprasert
- Clinical Epidemiology Unit, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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Chang Y, Liu Q, Zhou Z, Ding Y, Yang M, Xu W, Chen K, Zhang Q, Wang Z, Li H. Can Statin Treatment Reduce the Risk of Hepatocellular Carcinoma? A Systematic Review and Meta-Analysis. Technol Cancer Res Treat 2020; 19:1533033820934881. [PMID: 32552476 PMCID: PMC7307281 DOI: 10.1177/1533033820934881] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Revised: 02/24/2020] [Accepted: 03/30/2020] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Whether statins can reduce the incidence of cancers has been an interesting topic in recent years. This meta-analysis aimed to determine the relationship between statin treatment with the risk of hepatocellular carcinoma. METHODS Studies published up to July 2019 were screened from databases. The data from approved studies were pooled. Random-effects or fixed-effects model was used to calculate the relative risk with 95% CIs in the overall group and subgroups. Sensitivity and meta-regression analyses were performed, and publication bias was evaluated. RESULTS A total of 18 studies involving 1 611 596 patients were included in this meta-analysis. The overall result showed a significantly reduced risk of hepatocellular carcinoma (relative risk = 0.54, 95% CI: 0.42-0.66) in statin users. In comparison to the risk in nonstatin users, the risk of hepatocellular carcinoma was reduced in all subgroups. The dose of statins and their pharmacokinetics can partly explain the heterogeneity in the overall meta-analysis (I2 = 94.6%, P = .000). A dose-dependent effect of statin use for the reduced risk of hepatocellular carcinoma was found. CONCLUSIONS Findings from this meta-analysis support that statin use can significantly reduce the incidence of hepatocellular carcinoma.
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Affiliation(s)
- Yue Chang
- Department of Hepatopancreatobiliary and Splenic Medicine,
Characteristic Medical Center of People’s Armed Police Force, Tianjin, China
- Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular
Diagnosis and Treatment, Tianjin, China
| | - Qinyu Liu
- Department of Hepatopancreatobiliary and Splenic Medicine,
Characteristic Medical Center of People’s Armed Police Force, Tianjin, China
- Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular
Diagnosis and Treatment, Tianjin, China
| | - Zidong Zhou
- Department of Hepatopancreatobiliary and Splenic Medicine,
Characteristic Medical Center of People’s Armed Police Force, Tianjin, China
- Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular
Diagnosis and Treatment, Tianjin, China
| | - Yuping Ding
- Department of Hepatopancreatobiliary and Splenic Medicine,
Characteristic Medical Center of People’s Armed Police Force, Tianjin, China
- Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular
Diagnosis and Treatment, Tianjin, China
| | - Mei Yang
- Department of Hepatopancreatobiliary and Splenic Medicine,
Characteristic Medical Center of People’s Armed Police Force, Tianjin, China
- Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular
Diagnosis and Treatment, Tianjin, China
| | - Wei Xu
- Department of Hepatopancreatobiliary and Splenic Medicine,
Characteristic Medical Center of People’s Armed Police Force, Tianjin, China
- Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular
Diagnosis and Treatment, Tianjin, China
| | - Kai Chen
- Department of Hepatopancreatobiliary and Splenic Medicine,
Characteristic Medical Center of People’s Armed Police Force, Tianjin, China
- Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular
Diagnosis and Treatment, Tianjin, China
| | - Qing Zhang
- Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular
Diagnosis and Treatment, Tianjin, China
- Division of Gastroenterology and Hepatology, Tianjin Xiqing
Hospital, Tianjin, China
| | - Zhenguo Wang
- Department of Hepatopancreatobiliary and Splenic Medicine,
Characteristic Medical Center of People’s Armed Police Force, Tianjin, China
| | - Hai Li
- Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular
Diagnosis and Treatment, Tianjin, China
- Division of Gastroenterology and Hepatology, Tianjin Xiqing
Hospital, Tianjin, China
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Chou YC, Lin CH, Wong CS, Chou WY, Chang JY, Sun CA. Statin use and the risk of renal cell carcinoma: national cohort study. J Investig Med 2019; 68:776-781. [DOI: 10.1136/jim-2019-001209] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/22/2019] [Indexed: 12/29/2022]
Abstract
Statins are a therapeutic drug with reducing plasma cholesterol levels and have been linked with potential antitumor effects. However, epidemiological studies on statin use and renal cell carcinoma (RCC) risk have been inconsistent. This cohort study aimed to examine this association in an Asian population. We identified patients who filled initial prescriptions for statins in the inpatient and ambulatory care order files from Taiwan’s National Health Insurance Research Database between January 1, 1998 and December 31, 2005 as the statin users cohort (n=14,067). The comparison cohort comprised of patients who had not taken any statin in the previous years prior to January 1, 1998 or had used statins for less than 28 cumulative defined daily doses between January 1, 1998 and December 31, 2005 (n=56 268). The outcome of interest was pathologically verified RCC occurred between January 1, 1999 and December 31, 2013. The Fine-Gray competing risk model was fitted to estimate HRs accompanying 95% CI. Patients with the use of statins had a significantly lower risk of RCC as compared with the non-users cohort, yielding an adjusted HR of 0.64 (95% CI, 0.38 to 0.87). Moreover, we found a significant inverse association between cumulative statin use and the risk of RCC. Further, the inverse association between statin use and risk of RCC was evident in both sexes. This population-based cohort study provides longitudinal evidence that the use of statins was associated with a reduced risk of RCC.
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Cheung KS, Chan EW, Wong AYS, Chen L, Seto WK, Wong ICK, Leung WK. Statins Were Associated with a Reduced Gastric Cancer Risk in Patients with Eradicated Helicobacter Pylori Infection: A Territory-Wide Propensity Score Matched Study. Cancer Epidemiol Biomarkers Prev 2019; 29:493-499. [PMID: 31792089 DOI: 10.1158/1055-9965.epi-19-1044] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2019] [Revised: 10/08/2019] [Accepted: 11/25/2019] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Individuals may still develop gastric cancer even after Helicobacter pylori eradication. We aimed to investigate statin effect on gastric cancer development in H. pylori-eradicated subjects. METHODS All adult subjects who were prescribed clarithromycin-based triple therapy between 2003 and 2012 were identified in this retrospective cohort study utilizing a territory-wide electronic healthcare database. Patients were observed from index date of H. pylori therapy, and censored at gastric cancer diagnosis, death, or December 2015 (study end date). Statin use was defined as ≥180-day use after index date. Exclusion criteria included gastric cancer diagnosed within the first year after index date, previous gastric cancer or gastrectomy, and H. pylori treatment failure. Subdistribution hazard ratio (SHR) of gastric cancer with statins was calculated by competing risk regression with propensity score (PS) analysis matching 19 variables (age, sex, comorbidities, and other drug usage, including proton pump inhibitors, nonsteroidal anti-inflammatory drugs, aspirin, cyclooxygenase-2 inhibitors, and metformin). RESULTS During a median follow-up of 7.6 years (interquartile range = 5.1-10.3), 169 (0.27%) of 63,605 patients developed gastric cancer at an incidence rate of 3.5 per 10,000 person-years. Among 22,870 PS-matched subjects, statins were associated with a lower gastric cancer risk (SHR = 0.34; 95% confidence interval, 0.19-0.61), in a duration- and dose-response manner (P trend < 0.05). CONCLUSIONS Statins were associated with a lower gastric cancer risk in a duration- and dose-response manner among H. pylori-eradicated patients. IMPACT This study provides evidence on the additional benefits of statins as chemopreventive agents against gastric cancer among H. pylori-eradicated patients.
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Affiliation(s)
- Ka Shing Cheung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Esther W Chan
- Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong
| | - Angel Y S Wong
- Department of Non-communicable Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Lijia Chen
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Wai-Kay Seto
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Ian C K Wong
- Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong.,UCL School of Pharmacy, University College London, London, United Kingdom
| | - Wai K Leung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
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Lim J, Kang SY, Park HS. Low serum cholesterol as a risk factor for kidney and bladder cancer among Korean men: using a national cohort sample. Cancer Causes Control 2019; 30:1101-1102. [PMID: 31432296 DOI: 10.1007/s10552-019-01219-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2019] [Accepted: 08/11/2019] [Indexed: 01/24/2023]
Affiliation(s)
- Jisun Lim
- Department of Family Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Seo Young Kang
- Department of Family Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Hye Soon Park
- Department of Family Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea.
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Wang Y, Ren F, Song Z, Chen P, Liu S, Ouyang L. Statin use and the risk of ovarian and endometrial cancers: a meta-analysis. BMC Cancer 2019; 19:730. [PMID: 31340777 PMCID: PMC6657066 DOI: 10.1186/s12885-019-5954-0] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2018] [Accepted: 07/18/2019] [Indexed: 02/07/2023] Open
Abstract
Background The relationship between statin use and the risk of ovarian or endometrial cancer remains controversial. Here, we investigated the relationship between statin use and the risk of ovarian and endometrial cancers. Methods We conducted a meta-analysis using articles retrieved from the PubMed, Embase, and Web of Science databases. All original comparative studies published in English that were related to statin use and the risk of ovarian or endometrial cancer were included. Results This meta-analysis included 19 studies enrolling 1,999,362 female subjects and 19,849 cancer cases (7,948 ovarian cancer cases and 11,901 endometrial cancer cases). The overall analysis indicated that statin use did not significantly reduce the risk of ovarian cancer [relative risk (RR) = 0.88, 95% confidence interval (CI) 0.76–1.03, p = 0.12] or the risk of endometrial cancer (RR = 0.88, 95% CI 0.78–1.00, p = 0.05.) Subgroup analyses based on study type, percentage of cancer cases, study location, and quality of studies also supported our conclusions. No association was found between long-term statin use (> 5 years) and the risk of ovarian cancer (RR = 0.73, 95% CI 0.51–1.04, p = 0.08) or endometrial cancer (RR = 0.79, 95% CI 0.58–1.08, p = 0.14). Conclusions Statin use did not lower the risk of ovarian cancer or endometrial cancer. The long-term use of statins (> 5 years) was not associated with a reduction in the risk of ovarian or endometrial cancer. Electronic supplementary material The online version of this article (10.1186/s12885-019-5954-0) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Yizi Wang
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China
| | - Fang Ren
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China
| | - Zixuan Song
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China
| | - Peng Chen
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China
| | - Shuang Liu
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China
| | - Ling Ouyang
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China.
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Guercio V, Turati F, Bosetti C, Polesel J, Serraino D, Montella M, Libra M, Galfano A, La Vecchia C, Tavani A. Bladder cancer risk in users of selected drugs for cardiovascular disease prevention. Eur J Cancer Prev 2019; 28:76-80. [PMID: 29280915 DOI: 10.1097/cej.0000000000000419] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
The aim of this study was to investigate the relation between bladder cancer risk and the use of selected drugs for cardiovascular disease (CVD) prevention, such as aspirin, statins, and calcium channel blockers (CCBs). We analyzed data from a multicentric case-control study carried out in Italy between 2003 and 2014, including 690 bladder cancer cases and 665 hospital controls. Odds ratios (ORs) of bladder cancer and corresponding 95% confidence intervals (CIs) were estimated using unconditional multiple logistic regression models. The ORs for bladder cancer were 1.21 (95% CI: 0.87-1.68) for regular use of aspirin, 0.72 (95% CI: 0.54-0.97) for use of any CCBs, and 1.32 (95% CI: 0.87-1.99) for use of any statins. A slight inverse association was found with duration of use of CCBs, whereas no consistent association was found with duration of use, age at first use, and frequency for aspirin and statin use, or with indication of use for aspirin (as an analgesic or, for CVD prevention). No significant association was found for various combinations of drugs or for all drugs combined (OR=1.23, 95% CI: 0.31-4.85). Our data indicate the lack of a relevant association between the use of selected drugs for CVD prevention and bladder cancer risk, although suggest a potential favorable role for CCBs.
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Affiliation(s)
- Valentina Guercio
- Department of Clinical Sciences and Community Health, University of Milan
| | - Federica Turati
- Department of Clinical Sciences and Community Health, University of Milan.,Department of Medical Statistics, Biometry and Bioinformatics, National Cancer Institute
| | - Cristina Bosetti
- Department of Epidemiology, IRCCS - The Mario Negri Institute for Pharmacological Research
| | - Jerry Polesel
- Unit of Cancer Epidemiology, CRO Aviano National Cancer Institute, Aviano
| | - Diego Serraino
- Unit of Cancer Epidemiology, CRO Aviano National Cancer Institute, Aviano
| | - Maurizio Montella
- Unit of Epidemiology, Cancer Institute G. Pascale Foundation Naples, Naples
| | - Massimo Libra
- Laboratory of Translational Oncology and Functional Genomics, Section of General and Clinical Pathology and Oncology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | | | - Carlo La Vecchia
- Department of Clinical Sciences and Community Health, University of Milan
| | - Alessandra Tavani
- Department of Epidemiology, IRCCS - The Mario Negri Institute for Pharmacological Research
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Ho W, Choo DW, Wu YJ, Chan TF, Lin ZF. Statin Use and the Risk of Prostate Cancer in Ischemic Heart Disease Patients in Taiwan. Clin Pharmacol Ther 2019; 106:458-466. [PMID: 30801679 DOI: 10.1002/cpt.1408] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Accepted: 01/06/2019] [Indexed: 12/30/2022]
Abstract
Patients with ischemic heart disease (IHD) are more likely to be diagnosed with prostate cancer. Statins, which are widely used in such patients, are shown to modify the risk of prostate cancer. To clarify the association between statin use and the risk of prostate cancer among patients with higher risk of developing prostate cancer in Taiwan, a cohort of 26,628 men with IHD and aged between 55 and 100 were acquired from the National Health Insurance Research Database and followed over a period of 8 years. The risk of prostate cancer was calculated by time-dependent Cox regression model. Statin use was associated with significantly lower risk of both total and advanced prostate cancer (adjusted hazard ratio (HR): 0.719, 95% confidence interval (CI): 0.570-0.908; adjusted HR: 0.718, 95% CI: 0.530-0.972 respectively). In Taiwan IHD population, the reduction in risk of prostate cancer was observed in statin users as compared with nonusers.
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Affiliation(s)
- Wei Ho
- School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan.,Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Dan-Wei Choo
- School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan.,Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Yi-Jung Wu
- School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan.,Graduate Institute of Pharmaceutical Science, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Ting-Fang Chan
- School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Zhen-Fang Lin
- School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan.,Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan.,Graduate Institute of Pharmaceutical Science, College of Medicine, National Taiwan University, Taipei, Taiwan.,Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan
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Assessing the relationship between statin use and oncologic outcomes among men electing active surveillance for localized prostate cancer. Prostate Cancer Prostatic Dis 2019; 22:617-623. [PMID: 30996285 DOI: 10.1038/s41391-019-0147-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Revised: 03/06/2019] [Accepted: 03/24/2019] [Indexed: 11/08/2022]
Abstract
BACKGROUND This study aims to assess the effect of statin therapy on outcomes among men managed with active surveillance. METHODS This is a retrospective cohort study evaluating 635 men managed with active surveillance from 2005 to 2015 at a large, academic medical center. The primary endpoints of analyses are disease reclassification (i.e., change in volume or grade of cancer on subsequent biopsies after diagnosis), progression to definitive therapy with curative intent (i.e., surgery or radiotherapy), and surveillance failure-defined as the development of either biochemical failure after definitive therapy, metastases, or prostate cancer-specific mortality-among statin and non-statin users. Secondary analyses were performed to assess the effect of statin use on outcomes among men who progressed to definitive treatment. RESULTS Three hundred fifty-six (56.1%) patients in the cohort were on statin therapy at the initiation of surveillance. The median age was 66.7 and 63.3 years among statin and non-statin users, respectively. On univariate analysis, there were no differences in the rates of disease reclassification, progression to definitive treatment, and surveillance failure between the statin and non-statin users in the cohort (all p > 0.05). There was no difference in the rate of biochemical failure among men who progressed to definitive therapy when stratified by statin use (p = 0.89). Pathologic data were available for 105 men who progressed to radical prostatectomy while on surveillance at our institution. Duration of statin use (months) was inversely correlated with adverse pathology for radical prostatectomy on both univariate (OR: 0.99; 95% CI 0.98, 0.99; p = 0.03) and multivariate analysis (OR: 0.98; 95% CI 0.97, 0.99; p = 0.02). CONCLUSION Statin use was not associated with any clinical benefit with regard to disease reclassification, progression to definitive treatment, or surveillance failure among men selecting active surveillance at our institution. There was a 2% decrease in the odds of adverse pathology for each month of statin use among the men who progressed to radical prostatectomy while on active surveillance, but it is unclear at this time if this association has any durable impact on surveillance outcomes among men with favorable risk prostate cancer.
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Abstract
OBJECTIVE The aim of this study was to explore the relationship between statin use and the risk of pancreatic cancer. METHODS Electronic databases were searched to identify relevant studies published until January 2018. The pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated with random-effects model. Subgroup analyses and sensitivity analysis were also conducted. Cochran Q test and I(2) statistic were used to evaluate the heterogeneity. RESULTS Twenty-six studies were included that contained more than 3 million participants and 170,000 pancreatic cancer patients. The overall result demonstrated a significant decrease in pancreatic cancer risk with statin use (RR, 0.84; 95% CI, 0.73-0.97; P = 0.000; I(2) = 84.4%). In subgroup analyses, nonsignificant association was detected between long-term statin use and the risk of pancreatic cancer (RR, 0.98; 95% CI, 0.86-1.11; P = 0.718; I(2) = 0.0%). Meanwhile, there was nonsignificant association between the use of lipophilic statins and the risk of pancreatic cancer (RR, 0.98; 95% CI, 0.84-1.15; P = 0.853; I(2) = 27.2%). No publication bias was found in this meta-analysis. CONCLUSIONS The overall result of this meta-analysis supports the hypothesis that statins have a protective effect on pancreatic cancer. Furthermore, high-quality randomized clinical trials and cohort studies are needed to confirm these findings.
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Fowke JH, Motley SS. Statin use linked with a decrease in the conversion from high-grade prostatic intraepithelial neoplasia (HGPIN) to prostate cancer. Carcinogenesis 2019; 39:819-825. [PMID: 29617729 DOI: 10.1093/carcin/bgy050] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2017] [Accepted: 04/02/2018] [Indexed: 12/31/2022] Open
Abstract
The roles of obesity, metabolic dysregulation and systemic inflammation to advance prostate carcinogenesis are unclear. This study investigates metabolic and inflammatory factors in the transition from high-grade prostatic intraepithelial neoplasia (HGPIN) to prostate cancer (PC). We prospectively followed 160 men diagnosed with HGPIN at biopsy and therefore at high-risk and clinically monitored for PC. Analyses investigated body mass index (BMI), waist circumference, waist-hip ratio (WHR), height, fat mass, lean mass percent body fat, NSAIDs, statins, metformin, diabetes, hypertension, hypercholesterolemia representing metabolic dysregulation on the risk of a PC diagnosis during follow-up. Systemic inflammation was estimated through measurement of 13 plasma cytokine levels. Statin use was significantly linked with overall PC at follow-up [odds ratio (OR) = 0.45, (0.23, 0.91), P = 0.03], with a somewhat stronger link with high-grade [OR = 0.39, (0.15, 1.04), P = 0.06] PC compared with low-grade PC [OR = 0.50, (0.23, 1.12), P = 0.09]. Non-statin cholesterol-lowering medications, BMI, WHR, diabetes, hypertension and percent body fat were not significantly associated with PC. Although blood IL-12p70, IL-2 and IL-1β levels were significantly lower among statin users, inflammatory markers were not significantly linked with PC and did not explain the observed relationship between statins and lower PC risk. In summary, this prospective study of HGPIN patients at high risk for PC finds that statin use was significantly associated with reduced risk of PC detection at follow-up. Systemic markers of inflammation did not mediate this association, suggesting that statins affect PC progression through alternative pathways.
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Affiliation(s)
- Jay H Fowke
- Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.,Division of Epidemiology, Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Saundra S Motley
- Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
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Archibugi L, Arcidiacono PG, Capurso G. Statin use is associated to a reduced risk of pancreatic cancer: A meta-analysis. Dig Liver Dis 2019; 51:28-37. [PMID: 30314951 DOI: 10.1016/j.dld.2018.09.007] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2018] [Revised: 09/04/2018] [Accepted: 09/05/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND Previous studies investigating the association between statin use and pancreatic cancer (PDAC) risk for a possible chemopreventive effect gathered heterogeneous results. AIMS To conduct a systematic review and meta-analysis to clarify this association. METHODS Comprehensive literature search of articles published up to February 2018, including case-control (CC),cohort studies (C), randomized controlled trials (RCTs) assessing association between statin use and PDAC risk. Studies had to report odds ratio (OR)/relative risk (RR), estimates with 95% confidence interval (CI), or provide data for their calculation. Pooled ORs with 95%CIs were calculated using random effects model, publication bias through Begg and Mazumdar test and heterogeneity by I2 value. RESULTS 27 studies(13 CC, 9C, 5 RCTs) for a total population of 11,975 PDAC/3,433,175 controls contributed to the analysis. The overall pooled result demonstrated a reduced PDAC risk among statin users (OR 0.70; 95% CI 0.60-0.82; p < 0.0001), compared to non-users. Sensitivity analyses suggested the risk reduction to be more important in CC studies, studies conducted in Asia and Europe, in males and atorvastatin users. No publication bias found. CONCLUSIONS The present meta-analysis suggests that statin use is associated with an overall PDAC risk reduction of 30%. Further studies are needed to clarify the association.
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Affiliation(s)
- Livia Archibugi
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy
| | - Paolo Giorgio Arcidiacono
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy
| | - Gabriele Capurso
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy.
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Kim S, Lee M, Dhanasekaran DN, Song YS. Activation of LXRɑ/β by cholesterol in malignant ascites promotes chemoresistance in ovarian cancer. BMC Cancer 2018; 18:1232. [PMID: 30526541 PMCID: PMC6288854 DOI: 10.1186/s12885-018-5152-5] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2018] [Accepted: 11/29/2018] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND The purpose of this study was to investigate the role of malignant ascites tumor microenvironment in ovarian cancer progression and chemoresistance. METHODS A total of 45 patients with ovarian cancer and three benign ascites were collected at the time of clinical intervention. Ascites cholesterol levels were quantitated using cholesterol quantitation kit and recurrence free survival (RFS) of ovarian cancer patients were collected. The sensitivity of ovarian cancer cells to cisplatin (CDDP) and paclitaxel (PAC) were assessed by viability assay, flow cytometry and protein expression. Receiver operating characteristics (ROC) curve and Youden index analysis were applied to calculate the optimal cut-off values for ascites cholesterol. Kaplan-Meier curve were applied to compare RFS between high and low ascites cholesterol levels in ovarian cancer patients. RESULTS Here we show that cholesterol is elevated in malignant ascites and modulates the sensitivity of ovarian cancer cells to CDDP and PAC by upregulating the expression of drug efflux pump proteins, ABCG2 and MDR1, together with upregulation of LXRɑ/β, the cholesterol receptor. Transfection of LXRɑ/β siRNA inhibited cholesterol-induced chemoresistance and upregulation of MDR1. In addition, the cholesterol level in malignant ascites was negatively correlated with number of CDDP-induced apoptotic cell death, but not with that of PAC-induced apoptotic cell death. Cholesterol depletion by methyl beta cyclodextrin (MβCD) inhibited malignant ascites-induced chemoresistance to CDDP and upregulation of MDR1 and LXRɑ/β. For patients with ovarian cancer, high cholesterol level in malignant ascites correlated with short RFS. CONCLUSIONS High cholesterol in malignant ascites contributes to poor prognosis in ovarian cancer patients, partly by contributing to multidrug resistance through upregulation of MDR1 via activation of LXRɑ/β.
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Affiliation(s)
- Soochi Kim
- Seoul National University Hospital Biomedical Research Institute, Seoul, 03080 Republic of Korea
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, 03080 Republic of Korea
| | - Maria Lee
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, 03080 Republic of Korea
| | - Danny N. Dhanasekaran
- Stephenson Cancer Center, university of Oklahoma Health Sciences Center, Oklahoma City, OK 73012 USA
| | - Yong Sang Song
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, 03080 Republic of Korea
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, 03080 Republic of Korea
- Interdisciplinary Program in Cancer Biology, Seoul National University College of Medicine, Seoul, 03080 Republic of Korea
- Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul, 03080 Republic of Korea
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45
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Thomas T, Loke Y, Beales ILP. Systematic Review and Meta-analysis: Use of Statins Is Associated with a Reduced Incidence of Oesophageal Adenocarcinoma. J Gastrointest Cancer 2018; 49:442-454. [PMID: 28691139 PMCID: PMC6208835 DOI: 10.1007/s12029-017-9983-0] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
PURPOSE Laboratory studies have suggested that statins may have useful anti-cancer effects against Barrett's epithelial cancer lines. A variety of effects have been reported in clinical studies. METHODS We performed a systematic review and meta-analysis of the association between statin use and the development of oesophageal cancer. Multiple databases were searched for studies reporting the association of statin use and oesophageal cancer. Meta-analysis on the relationship between statin use and cancer incidence was performed. RESULTS Twenty publications met eligibility criteria, yielding 22 datasets for meta-analysis. All were observational studies. Population-level studies included 372,206 cancer cases and 6,086,906 controls. Studies examining adenocarcinoma development in Barrett's oesophagus included 1057 cancers and 17,741 controls. In patients with Barrett's oesophagus, statin use was associated with a reduced incidence of adenocarcinoma (pooled adjusted odds ratio (OR) 0.59 (95% confidence intervals 0.50-0.68)), with no heterogeneity between 11 studies. Population-based studies demonstrated more heterogeneity but showed that statin use was associated with a lower incidence of both oesophageal adenocarcinoma (OR 0.57 (0.43-0.76)) and all oesophageal cancers (OR 0.82 (0.7-0.88)). Information on statin type, dose, and duration was reported too infrequently for statistical analysis but individual studies showed a tendency to a dose- and duration-dependant decrease in cancer incidence. CONCLUSIONS Statin use is associated with a significantly lower incidence of oesophageal adenocarcinoma. This is seen in both Barrett's cohorts and general populations. Further studies should focus on drug, dose, and duration and the interaction with other risk and preventative factors.
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Affiliation(s)
- Tom Thomas
- Norwich Medical School, University of East Anglia, Norwich, NR4 TJ, UK
| | - Yoon Loke
- Norwich Medical School, University of East Anglia, Norwich, NR4 TJ, UK
| | - Ian L P Beales
- Norwich Medical School, University of East Anglia, Norwich, NR4 TJ, UK.
- Department of Gastroenterology, Norfolk and Norwich University Hospital, Norwich, NR4 7UY, UK.
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Jang HJ, Kim HS, Kim JH, Lee J. The Effect of Statin Added to Systemic Anticancer Therapy: A Meta-Analysis of Randomized, Controlled Trials. J Clin Med 2018; 7:jcm7100325. [PMID: 30287761 PMCID: PMC6210992 DOI: 10.3390/jcm7100325] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2018] [Revised: 09/25/2018] [Accepted: 10/02/2018] [Indexed: 12/19/2022] Open
Abstract
Preclinical studies have demonstrated that statins have anticancer properties and act in an additive or synergistic way when combined with anticancer therapy. We conducted this meta-analysis of randomized, controlled phase II or III trials to evaluate the effect of statins added to systemic anticancer therapy in patients with solid cancer. A systematic literature search was performed to identify all randomized trials that were designed to investigate the effect of statins in patients with cancer using PubMed, EMBASE, Google Scholar, and Web of Science (up to August 2018). From eight randomized controlled trials, 1760 patients were included in the pooled analyses of odds ratios (ORs) with 95% confidence intervals (CIs) for grade 3–5 adverse events (AEs) and overall response rate (ORR) and hazard ratios (HRs) with 95% CIs for progression-free survival (PFS) and overall survival (OS). The addition of statin to anticancer agents did not significantly increase the incidence of grade 3–5 AEs (OR = 1.03, 95% CI: 0.81–1.29, p = 0.78). However, the combination of statin and anticancer agents did not improve ORR (OR = 0.96, 95% CI: 0.77–1.20, p = 0.72) compared with that of anticancer therapy alone. In addition, statins added to systemic anticancer therapy failed to prolong PFS (HR = 0.99, 95% CI: 0.90–1.10, p = 0.92) and OS (HR = 0.91, 95% CI: 0.76–1.11, p = 0.52). In conclusion, this meta-analysis of randomized controlled trials does not support clinical benefits of statins added to systemic anticancer therapy in patients with solid cancer.
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Affiliation(s)
- Hyun Joo Jang
- Division of Gastroenterology, Department of Internal Medicine, Dongtan Sacred-Heart Hospital, Hallym University Medical Center, Hallym University College of Medicine, Hwasung 18450, Gyeonggi-Do, Korea.
| | - Hyeong Su Kim
- Division of Hemato-Oncology, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Seoul 07441, Korea.
| | - Jung Han Kim
- Division of Hemato-Oncology, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Seoul 07441, Korea.
| | - Jin Lee
- Division of Gastroenterology, Department of Internal Medicine, Dongtan Sacred-Heart Hospital, Hallym University Medical Center, Hallym University College of Medicine, Hwasung 18450, Gyeonggi-Do, Korea.
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Cheung KS, Leung WK. Risk of gastric cancer development after eradication of Helicobacter pylori. World J Gastrointest Oncol 2018; 10:115-123. [PMID: 29770171 PMCID: PMC5952268 DOI: 10.4251/wjgo.v10.i5.115] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2018] [Revised: 03/23/2018] [Accepted: 04/16/2018] [Indexed: 02/05/2023] Open
Abstract
Helicobacter pylori (H. pylori) infection is the most important risk factor for gastric cancer (GC) development through the Correa’s gastric carcinogenesis cascade. However, H. pylori eradication alone does not eliminate GC, as pre-neoplastic lesions (atrophic gastritis, intestinal metaplasia and dysplasia) may have already developed in some patients. It is therefore necessary to identify patients at high-risk for gastric cancer after H. pylori eradication to streamline the management plan. If the patients have not undergone endoscopy with histologic assessment, the identification of certain clinical risk factors and non-invasive testing (serum pepsinogen) can predict the risk of atrophic gastritis. For those with suspected atrophic gastritis, further risk stratification by endoscopy with histologic assessment according to validated histologic staging systems would be advisable. Patients with higher stages may require long-term endoscopic surveillance. Apart from secondary prevention to reduce deaths by diagnosing GC at an early stage, identifying medications that could potentially modify the GC risk would be desirable. The potential roles of a number of medications have been suggested by various studies, including proton pump inhibitors (PPIs), aspirin, statins and metformin. However, there are currently no randomized clinical trials to address the impact of these medications on GC risk after H. pylori eradication. In addition, most of these studies failed to adjust for the effect of concurrent medications on GC risk. Recently, large population-based retrospective cohort studies have shown that PPIs were associated with an increased GC risk after H. pylori eradication, while aspirin was associated with a lower risk. The roles of other agents in reducing GC risk after H. pylori eradication remain to be determined.
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Affiliation(s)
- Ka-Shing Cheung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
| | - Wai K Leung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
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Ye X, Zhang G, Righolt C, Johnston JB, Banerji V, Gibson SB, Mahmud SM. Associations between statin use and risk of non-Hodgkin lymphomas by subtype. Int J Cancer 2018. [PMID: 29524215 DOI: 10.1002/ijc.31373] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Non-Hodgkin lymphomas (NHL) are a group of cancers with highly heterogeneous biology and clinical features. Statins are increasingly prescribed to prevent cardiovascular diseases. Early evidence shows a preventive effect of statins for some cancers, but their effect on NHL risk is unclear. We conducted a population-based nested case-control study involving 5,541 NHL cases and 27,315 controls matched for gender, age, place of residence and length of period of available prescription drug data. We assessed the use of statins prior to diagnosis (excluding the 12 months prior to the index date). We used conditional logistic regression models to estimate odds ratio (OR) and 95% confidence interval (CI) for use of any statin, adjusting for medical conditions, number of family physician visits for 5 years prior to index date, healthcare utilization, income and use of other medications. Over one-quarter of cases and controls were prescribed statins. Ever-use of any statin was associated with lower risk of Total NHL (OR = 0.82, 95% CI 0.76-0.89) and of certain subtypes including diffuse large B-cell lymphomas (DLBCL, OR = 0.77, 95% CI 0.65-0.92), plasma cell neoplasms (PCN, OR = 0.76, 95% CI 0.63-0.91) and other B-cell NHL (0.75, 0.59-0.95). Analysis by statin type suggested that the association was limited to high potency statin and lipophilic statin users. No clear duration or dose-response relationships were observed. Our findings provide evidence that statin use can reduce the risk of DLBCL and plasma cell lymphomas, but not other NHL types. Further studies are warranted to verify these associations and to examine the biological mechanisms.
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Affiliation(s)
- Xibiao Ye
- Department of Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada
- Vaccine and Drug Evaluation Centre, University of Manitoba, Winnipeg, MB, Canada
| | - Geng Zhang
- Department of Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada
- Vaccine and Drug Evaluation Centre, University of Manitoba, Winnipeg, MB, Canada
| | - Christiaan Righolt
- Department of Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada
- Vaccine and Drug Evaluation Centre, University of Manitoba, Winnipeg, MB, Canada
| | - James B Johnston
- Research Institute of Oncology and Hematology, Cancer Care Manitoba, Winnipeg, MB, Canada
- Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada
| | - Versha Banerji
- Research Institute of Oncology and Hematology, Cancer Care Manitoba, Winnipeg, MB, Canada
- Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada
| | - Spencer B Gibson
- Research Institute of Oncology and Hematology, Cancer Care Manitoba, Winnipeg, MB, Canada
- Department of Immunology, University of Manitoba, Winnipeg, MB, Canada
- Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada
| | - Salaheddin M Mahmud
- Department of Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada
- Vaccine and Drug Evaluation Centre, University of Manitoba, Winnipeg, MB, Canada
- College of Pharmacy, University of Manitoba, Winnipeg, MB, Canada
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Dawe DE, Ye X, Czaykowski P, Jassal D, Singh H, Skarsgard D, Aprikian A, Mahmud SM. The effect of statin use on the incidence of prostate cancer: A population-based nested case-control study. Int J Cancer 2018; 143:190-198. [PMID: 29405283 DOI: 10.1002/ijc.31295] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2017] [Revised: 11/28/2017] [Accepted: 12/19/2017] [Indexed: 11/11/2022]
Abstract
Preclinical studies suggest statins may help prevent prostate cancer (PC), but epidemiologic results are mixed. Many epidemiological studies have relatively short prediagnosis drug exposure data, which may miss some statin use. We completed a nested case-control study investigating the impact of statin use on PC diagnosis and clinically significant PC using data from men aged ≥40 years in the Canadian province of Saskatchewan between 1990 and 2010. Drug exposure histories were derived from a population-based prescription drug database. We used conditional logistic regression to model use of statins as a class and stratified analyses for groups defined by lipophilicity. Clinically significant PC was defined as Gleason score 8-10 OR stage C or D or III or IV at diagnosis. 12,745 cases of PC were risk-set matched on age and geographic location to 50,979 controls. Greater than 90% of subjects had prediagnosis drug exposure histories >15 years. 2,064 (16.2%) cases and 7,956 (15.6%) controls were dispensed one or more statin prescriptions. In multivariable models, ever prescription of statins was not associated with PC diagnosis (OR 0.97; 95% CI 0.90-1.05). Neither lipophilic statins (OR 0.96, 95% CI 0.88-1.04) nor hydrophilic statins (OR 1.06, 95% CI 0.95-1.20) impacted PC diagnosis. There was no effect of the dose or duration of statin use. Diagnosis of clinically significant PC decreased with statin use (OR 0.84, 95% CI 0.73-0.97). Statin use is not associated with overall PC risk, regardless of duration or dose of statin exposure. Statin use is associated with a decreased risk of clinically significant PC.
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Affiliation(s)
- David E Dawe
- Department of Hematology and Medical Oncology, CancerCare Manitoba, Winnipeg, Manitoba, Canada.,Faculty of Health Sciences, Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Xibiao Ye
- Faculty of Health Sciences, Department of Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Piotr Czaykowski
- Department of Hematology and Medical Oncology, CancerCare Manitoba, Winnipeg, Manitoba, Canada.,Faculty of Health Sciences, Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.,Faculty of Health Sciences, Department of Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Davinder Jassal
- Department of Hematology and Medical Oncology, CancerCare Manitoba, Winnipeg, Manitoba, Canada.,Faculty of Health Sciences, Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Harminder Singh
- Department of Hematology and Medical Oncology, CancerCare Manitoba, Winnipeg, Manitoba, Canada.,Faculty of Health Sciences, Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.,Faculty of Health Sciences, Department of Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
| | - David Skarsgard
- Department of Oncology, University of Calgary, Calgary, Alberta, Canada
| | - Armen Aprikian
- Department of Oncology, McGill University, Montreal, Quebec, Canada
| | - Salaheddin M Mahmud
- Faculty of Health Sciences, Department of Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.,Department of Epidemiology and Cancer Registry, CancerCare Manitoba, Winnipeg, Manitoba, Canada
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An analysis of the association between statin use and risk of endometrial and ovarian cancers in the Women's Health Initiative. Gynecol Oncol 2018; 148:540-546. [PMID: 29422345 DOI: 10.1016/j.ygyno.2018.01.006] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2017] [Revised: 01/04/2018] [Accepted: 01/05/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Statins have anti proliferative activity in vitro against endometrial and ovarian cancer and can affect levels of reproductive hormones. We analyzed data from the Women's Health Initiative (WHI) to assess whether statins are associated with risk of endometrial and ovarian cancer. METHODS The WHI study included 161,808 postmenopausal women in which incident cases of endometrial (n = 1377) and ovarian cancer (n = 763) were identified over an average of 10.8 (SD + 3.3) years. Information on statin use and risk factors was collected at baseline and follow-up. Cox proportional hazards regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for the association of statin use and risk of endometrial and ovarian cancer. All statistical tests were two-sided. RESULTS Statins were used at baseline by 7.5% women and by up to 25% at year nine. The multivariable adjusted HR for risk of endometrial cancer for baseline statin use was 0.74, 95% C.I. 0.59-0.94 and for ovarian cancer was 1.15, 95% C.I. 0.89-1.50. In time-dependent models, statins were not associated with endometrial cancer (HR 0.91, 95% C.I. 0.76-1.08) however there was an increased risk of ovarian cancer (HR 1.30, 95% CI 1.04-1.62), largely attributed to the effect of the hydrophilic statin, pravastatin (1.89, 95% CI 1.24-2.88). CONCLUSIONS There was a reduction in risk of endometrial cancer among statin users at baseline but not in time-dependent models. Pravastatin use was associated with an increased risk of ovarian cancer. Analyses of larger numbers of cases are needed to evaluate these findings.
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