Generic placeholder image

Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Systematic Review Article

The Relationship Between Prostate Cancer and Metformin Consumption: A Systematic Review and Meta-analysis Study

Author(s): Bahareh Ghiasi, Diana Sarokhani*, Farid Najafi, Morteza Motedayen and Ali Hasanpour Dehkordi*

Volume 25, Issue 9, 2019

Page: [1021 - 1029] Pages: 9

DOI: 10.2174/1381612825666190215123759

Price: $65


Introduction: Prostate cancer is the most common malignant cancer in men worldwide and after lung cancer, it is the second leading cause of cancer mortality in men. The purpose of this study was to investigate the relationship between prostate cancer and metformin consumption in men.

Methods: The current study is a systematic and meta-analysis review based on the PRISMA statement. To access the studies of domestic and foreign databases, Iran Medex, SID, Magiran, Iran Doc, Medlib, ProQuest, Science Direct, PubMed, Scopus, Web of Science and the Google Scholar search engine were searched during the 2009- 2018 period for related keywords. In order to evaluate the heterogeneity of the studies, Q test and I2 indicator were used. The data were analyzed using the STATA 15.1 software.

Results: In 11 studies with a sample size of 877058, the odds ratio of metformin consumption for reducing prostate cancer was estimated at 0.89 (95%CI: 0.67-1.17). Meta-regression also showed there was no significant relationship between the odds ratio and the publication year of the study. However, there was a significant relationship between the odds ratio and the number of research samples.

Conclusion: Using metformin in men reduces the risk of prostate cancer but it is not statistically significant.

Keywords: Metformin, prostate cancer, chronic diseases, I2 indicator, lung cancer, Q test.

Next »
Baguley BJ, Bolam KA, Wright ORL, Skinner TL. The effect of nutrition therapy and exercise on cancer-related fatigue and quality of life in men with prostate cancer: a systematic review. Nutrients 2017; 9(9): 1003. []. [PMID: 28895922].
Noghabi AAA, Zandi M, Mehran A, Alavian SM, Dehkordi AH. The effect of education on quality of life in patients under interferon therapy. Hepat Mon 2010; 10(3): 218-22. [PMID: 22308142].
Mokhtari Z, Gheshlagh RG, Kurdi A. Health-related quality of life in Iranian patients with type 2 diabetes: An updated meta-analysis. Diabetes Metab Syndr 2019; 13(1): 402-7. []. [PMID: 30641733].
Hasanpour Dehkordi A. Influence of yoga and aerobics exercise on fatigue, pain and psychosocial status in patients with multiple sclerosis: a randomized trial. J Sports Med Phys Fitness 2016; 56(11): 1417-22. [PMID: 26223004].
Hasanpour-Dehkordi A, Jivad N, Solati K. Effects of yoga on physiological indices, anxiety and social functioning in multiple sclerosis patients: a randomized trial. J Clin Diagn Res 2016; 10(6): VC01-5. [PMID: 27504387].
Salarvand S, Hemati S, Adibi P, Taleghani F, Gheshlagh RG. Evaluation of the Quality of Cancer-Related Fatigue Clinical Practice Guidelines. Evidence Based Care 2018; 8(3): 64-74. [].
Grubb RL III, Kibel AS. Prostate cancer: screening, diagnosis and management in 2007. Mo Med 2007; 104(5): 408-13. [PMID: 18018527].
Simon H. The Harvard Medical School Guide to Men’s Health: Lessons from the Harvard Men’s Health Studies. Free Press 2004.
Pourmand G, Salem S, Mehrsai A, et al. The risk factors of prostate cancer: a multicentric case-control study in Iran. Asian Pac J Cancer Prev 2007; 8(3): 422-8. [PMID: 18159981].
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68(6): 394-424. []. [PMID: 30207593].
Fitzmaurice C, Akinyemiju TF, Al Lami FH, et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 29 cancer groups, 1990 to 2016: a systematic analysis for the global burden of disease study. JAMA Oncol 2018; 4(11): 1553-68. []. [PMID: 29860482].
Pinsky PF, Prorok PC, Yu K, et al. Extended mortality results for prostate cancer screening in the PLCO trial with median follow-up of 15 years. Cancer 2017; 123(4): 592-9. []. [PMID: 27911486].
Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin 2014; 64(1): 9-29. []. [PMID: 24399786].
Nebert DW, McKinnon RA, Puga A. Human drug-metabolizing enzyme polymorphisms: effects on risk of toxicity and cancer. DNA Cell Biol 1996; 15(4): 273-80. []. [PMID: 8639263].
Hsing AW, Sakoda LC, Chua S Jr. Obesity, metabolic syndrome, and prostate cancer. Am J Clin Nutr 2007; 86(3): s843-57. []. [PMID: 18265478].
Jackson MD, Walker SP, Simpson-Smith CM, et al. Associations of whole-blood fatty acids and dietary intakes with prostate cancer in Jamaica. Cancer Causes Control 2012; 23(1): 23-33. []. [PMID: 21984307].
Ferlay J, Bray F, Pisani P, Parkin D. Cancer incidence, mortality and prevalence worldwide. IARC Cancer Base 2002; p. 5.
Hsing AW, Chokkalingam AP. Prostate cancer epidemiology. Front Biosci 2006; 11(5): 1388-413. []. [PMID: 16368524].
Mallick S, Blanchet P, Multigner L. Prostate cancer incidence in guadeloupe, a French Caribbean archipelago. Eur Urol 2005; 47(6): 769-72. []. [PMID: 15925071].
Currie CJ, Poole CD, Jenkins-Jones S, Gale EA, Johnson JA, Morgan CL. Mortality after incident cancer in people with and without type 2 diabetes: impact of metformin on survival. Diabetes Care 2012; 35(2): 299-304. []. [PMID: 22266734].
Turini M, Redaelli A, Gramegna P, Radice D. Quality of life and economic considerations in the management of prostate cancer. Pharmacoeconomics 2003; 21(8): 527-41. []. [PMID: 12751912].
Center MM, Jemal A, Lortet-Tieulent J, et al. International variation in prostate cancer incidence and mortality rates. Eur Urol 2012; 61(6): 1079-92. []. [PMID: 22424666].
Breslow N, Chan C, Dhom G, et al. Latent carcinoma of the prostate atautopsy in seven areas. Int J Cancer 1977; 20(5): 680-8. []. [PMID: 924691].
Jemal A, Center MM, DeSantis C, Ward EM. Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev 2010; 19(8): 1893-907. []. [PMID: 20647400].
Greiman AK, Rosoff JS, Prasad SM. Association of Human Development Index with global bladder, kidney, prostate and testis cancer incidence and mortality. BJU Int 2017; 120(6): 799-807. []. [PMID: 28480994].
Carter H, Partin A. Diagnosis and staging of prostate cancer Campbell’ Urology. Philadelphia: WB Saunders 2002; pp. 3055-79.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011; 61(2): 69-90. []. [PMID: 21296855].
Cotran Ramzi S, Kumar V, Collins T. Disease of ImmunityCotran, Ramzi S, Kumar V, Collins T Robbins Pathologic Basis of Disease. 6th ed. Philadelphia: W B Saunders 1999; pp. 188-259.
Khoshgard K, Rahimi SA. Comparison of radiation absorbed dose received by bladder and rectum between conventional and conformal treatment planning methods in radiotherapy of prostate cancer. J Med Sci 2014; 14(4): 162-7. [].
Pollak M. Metformin and other biguanides in oncology: advancing the research agenda. Cancer Prev Res (Phila) 2010; 3(9): 1060-5. []. [PMID: 20810670].
Margel D, Urbach D, Lipscombe LL, et al. Association between metformin use and risk of prostate cancer and its grade. J Natl Cancer Inst 2013; 105(15): 1123-31. []. [PMID: 23853056].
Ben Sahra I, Laurent K, Loubat A, et al. The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level. Oncogene 2008; 27(25): 3576-86. []. [PMID: 18212742].
Prabhakaran S, Thirumal D, Gimbun J, Ranganathan B. Metformin-A Panacea Pharmaceutical Agent through convergence revolution initiative. J Nat Rem 2018; 17(3): 69-79. [].
Huang X, Wullschleger S, Shpiro N, et al. Important role of the LKB1-AMPK pathway in suppressing tumorigenesis in PTEN-deficient mice. Biochem J 2008; 412(2): 211-21. []. [PMID: 18387000].
Niehr F, von Euw E, Attar N, et al. Combination therapy with vemurafenib (PLX4032/RG7204) and metformin in melanoma cell lines with distinct driver mutations. J Transl Med 2011; 9: 76. []. [PMID: 21609436].
Rozengurt E, Sinnett-Smith J, Kisfalvi K. Crosstalk between insulin/insulin-like growth factor-1 receptors and G protein-coupled receptor signaling systems: a novel target for the antidiabetic drug metformin in pancreatic cancer. Clin Cancer Res 2010; 16(9): 2505-11. []. [PMID: 20388847].
Hasanvand A. Antioxidative and anti-inflammatory effects of metformin; a new look to an old drug. J Renal Endocrinol 2018; 4: e02.
Mallik R, Chowdhury TA. Metformin in cancer. Diabetes Res Clin Pract 2018; 143: 409-19. []. [PMID: 29807101].
Li D, Yeung SC, Hassan MM, Konopleva M, Abbruzzese JL. Antidiabetic therapies affect risk of pancreatic cancer. Gastroenterology 2009; 137(2): 482-8. []. [PMID: 19375425].
Nasri H. A short look to the nephroprotective impacts of metformin. Toxicologia Persa 2016; 1(1): e01.
Whitburn J, Edwards CM, Sooriakumaran P. Metformin and prostate cancer: a new role for an old drug. Curr Urol Rep 2017; 18(6): 46. []. [PMID: 28444639].
Bailey CJ. Biguanides and NIDDM. Diabetes Care 1992; 15(6): 755-72. []. [PMID: 1600835].
Sumida Y, Seko Y, Yoneda M. Novel antidiabetic medications for non-alcoholic fatty liver disease with type 2 diabetes mellitus. Hepatol Res 2017; 47(4): 266-80. []. [PMID: 28019064].
Wiernsperger N. Metformin as a cellular protector; a synoptic view of modern evidences. J Nephropharmacol 2015; 4(1): 31-6. [PMID: 28197472].
Clements A, Gao B, Yeap SH, Wong MK, Ali SS, Gurney H. Metformin in prostate cancer: two for the price of one. Ann Oncol 2011; 22(12): 2556-60. []. [PMID: 21421541].
Tseng C-H. Metformin significantly reduces incident prostate cancer risk in Taiwanese men with type 2 diabetes mellitus. Eur J Cancer 2014; 50(16): 2831-7. []. [PMID: 25201464].
Morales DR, Morris AD. Metformin in cancer treatment and prevention. Annu Rev Med 2015; 66: 17-29. []. [PMID: 25386929].
Venkateswaran V, Haddad AQ, Fleshner NE, et al. Association of diet-induced hyperinsulinemia with accelerated growth of prostate cancer (LNCaP) xenografts. J Natl Cancer Inst 2007; 99(23): 1793-800. []. [PMID: 18042933].
Zakikhani M, Dowling RJ, Sonenberg N, Pollak MN. The effects of adiponectin and metformin on prostate and colon neoplasia involve activation of AMP-activated protein kinase. Cancer Prev Res (Phila) 2008; 1(5): 369-75. []. [PMID: 19138981].
Ben Sahra I, Laurent K, Loubat A, et al. The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level. Oncogene 2008; 27(25): 3576-86. []. [PMID: 18212742].
Wang W, Guan KL. AMP-activated protein kinase and cancer. Acta Physiol (Oxf) 2009; 196(1): 55-63. []. [PMID: 19243571].
Moher D, Shamseer L, Clarke M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 2015; 4: 1-9. []. [PMID: 25554246].
von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Ann Intern Med 2007; 147(8): 573-7. []. [PMID: 17938396].
Chen CB, Eurich DT, Majumdar SR, Johnson JA. Metformin and the risk of prostate cancer across racial/ethnic groups: a population-based cohort study. Prostate Cancer Prostatic Dis 2017; 20(1): 122-6. []. [PMID: 28071672].
Kabarriti A, Boursi B, Mamatani R, Guzzo T, Haynes K, Yang Y. Effect of metformin use on prostat cancer
Randazzo M, Hermanns T, Poyet C, et al. Association Of Metformin Use With Prostat Cancer Incidence In A Prospective screening Trial Erspc Arau 2015; 193(4): 1078.
Preston MA, Riis AH, Ehrenstein V, et al. Metformin use and prostate cancer risk. Eur Urol 2014; 66(6): 1012-20. []. [PMID: 24857538].
Tseng CH. Metformin significantly reduces incident prostate cancer risk in Taiwanese men with type 2 diabetes mellitus. Eur J Cancer 2014; 50(16): 2831-7. []. [PMID: 25201464].
Feng T, Sun X, Howard LE, et al. Metformin use and risk of prostate cancer: results from the REDUCE study. Cancer Prev Res (Phila) 2015; 8(11): 1055-60. []. [PMID: 26353947].
Wright JL, Stanford JL. Metformin use and prostate cancer in Caucasian men: results from a population-based case-control study. Cancer Causes Control 2009; 20(9): 1617-22. []. [PMID: 19653109].
Azoulay L, Dell’Aniello S, Gagnon B, Pollak M, Suissa S. Metformin and the incidence of prostate cancer in patients with type 2 diabetes. Cancer Epidemiol Biomarkers Prev 2011; 20(2): 337-44. []. [PMID: 21148757].
Morden NE, Liu SK, Smith J, Mackenzie TA, Skinner J, Korc M. Further exploration of the relationship between insulin glargine and incident cancer: a retrospective cohort study of older Medicare patients. Diabetes Care 2011; 34(9): 1965-71. []. [PMID: 21775752].
Home PD, Kahn SE, Jones NP, Noronha D, Beck-Nielsen H, Viberti G. Experience of malignancies with oral glucose-lowering drugs in the randomised controlled ADOPT (A Diabetes Outcome Progression Trial) and RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycaemia in Diabetes) clinical trials. Diabetologia 2010; 53(9): 1838-45. []. [PMID: 20532476].
Decensi A, Puntoni M, Goodwin P, et al. Metformin and cancer risk in diabetic patients: a systematic review and meta-analysis. Cancer Prev Res (Phila) 2010; 3(11): 1451-61. []. [PMID: 20947488].
Franciosi M, Lucisano G, Lapice E, Strippoli GF, Pellegrini F, Nicolucci A. Metformin therapy and risk of cancer in patients with type 2 diabetes: systematic review. PLoS One 2013; 8(8): e71583. []. [PMID: 23936520].
Wu L, Zhu J, Prokop LJ, Murad MH. Pharmacologic Therapy of Diabetes and Overall Cancer Risk and Mortality: A Meta-Analysis of 265 Studies. Sci Rep 2015; 5: 10147. []. [PMID: 26076034].
Zhu N, Zhang Y, Gong YI, He J, Chen X. Metformin and lung cancer risk of patients with type 2 diabetes mellitus: A meta-analysis. Biomed Rep 2015; 3(2): 235-41. []. [PMID: 26075077].
Śmieszek A, Stręk Z, Kornicka K, Grzesiak J, Weiss C, Marycz K. Antioxidant and anti-senescence effect of metformin on mouse olfactory ensheathing cells (mOECs) may be associated with increased brain-derived neurotrophic factor levels-an ex vivo study. Int J Mol Sci 2017; 18(4): 872. []. [PMID: 28425952].
Khodadadi S. Administration of Galega officinalis in experimental and clinical investigations; a narrative review. Ann Res Antioxid 2016; 1(1): e03.
Chukwunonso Obi B, Chinwuba Okoye T, Okpashi VE, Nonye Igwe C, Olisah Alumanah E. Comparative study of the antioxidant effects of metformin, glibenclamide, and repaglinide in alloxan-induced diabetic rats. J Diabetes Res 2016; 2016: 1635361. []. [PMID: 26824037].
Kocer D, Bayram F, Diri H. The effects of metformin on endothelial dysfunction, lipid metabolism and oxidative stress in women with polycystic ovary syndrome. Gynecol Endocrinol 2014; 30(5): 367-71. []. [PMID: 24517721].
Driver C, Hayangah J, Nyane N, Owira P. Metformin with insulin relieves oxidative stress and confers renoprotection in type 1 diabetes in vivo. J Nephropathol 2017; 7(3): 171-81. [].
Markowicz-Piasecka M, Sikora J, Szydlowska A, Skupien A, Mikiciuk-Olasik E, Huttuhen KM. Metformin–a future therapy for neurodegenerative diseases. Pharm Res 2017; 34(12): 2614-27. []. [PMID: 28589443].
Moradi Joo M, Mohabbat Bahar S, Heidari S, Davoodi S, Gareh Sheyklo S, Esmaeil Akbari M. Metformin versus sulfonylurea in breast cancer risk of diabetic patients: a systematic review and meta-analysis. Iran J Cancer Prev 2016; 9(5): 5971. [].
Soffer D, Shi J, Chung J, et al. Metformin and breast and gynecological cancer risk among women with diabetes. BMJ Open Diabetes Res Care 2015; 3(1): e000049. []. [PMID: 25664181].
Evans JM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD. Metformin and reduced risk of cancer in diabetic patients. BMJ 2005; 330(7503): 1304-5. []. [PMID: 15849206].
Chong CR, Chabner BA. Mysterious metformin. Oncologist 2009; 14(12): 1178-81. []. [PMID: 20007645].
Lee MS, Hsu CC, Wahlqvist ML, Tsai HN, Chang YH, Huang YC. Type 2 diabetes increases and metformin reduces total, colorectal, liver and pancreatic cancer incidences in Taiwanese: a representative population prospective cohort study of 800,000 individuals. BMC Cancer 2011; 11: 20. []. [PMID: 21241523].
Rattan R, Graham RP, Maguire JL, Giri S, Shridhar V. Metformin suppresses ovarian cancer growth and metastasis with enhancement of cisplatin cytotoxicity in vivo. Neoplasia 2011; 13(5): 483-91. []. [PMID: 21532889].
Shahreza FD. From oxidative stress to endothelial cell dysfunction. J Prev Med 2016; 1(1)
Zhang ZJ, Zheng ZJ, Kan H, et al. Reduced risk of colorectal cancer with metformin therapy in patients with type 2 diabetes: a meta-analysis. Diabetes Care 2011; 34(10): 2323-8. []. [PMID: 21949223].
Zhang ZJ, Zheng ZJ, Shi R, Su Q, Jiang Q, Kip KE. Metformin for liver cancer prevention in patients with type 2 diabetes: a systematic review and meta-analysis. J Clin Endocrinol Metab 2012; 97(7): 2347-53. []. [PMID: 22523334].
Ma S, Zheng Y, Xiao Y, Zhou P, Tan H. Meta-analysis of studies using metformin as a reducer for liver cancer risk in diabetic patients. Medicine (Baltimore) 2017; 96(19): e6888. []. [PMID: 28489794].
Hong H, Yong F, Xiaoyun Z, et al. Relationship of metformin with the risk of pancreatic cancer in patients with type 2 diabetes: a meta-analysis. Biomed Res (Aligarh) 2017; 28(10): 4439-44.
Gandini S, Puntoni M, Heckman-Stoddard BM, et al. Metformin and cancer risk and mortality: a systematic review and meta-analysis taking into account biases and confounders. Cancer Prev Res (Phila) 2014; 7(9): 867-85. []. [PMID: 24985407].
Deng D, Yang Y, Tang X, et al. Association between metformin therapy and incidence, recurrence and mortality of prostate cancer: evidence from a meta-analysis. Diabetes Metab Res Rev 2015; 31(6): 595-602. []. [PMID: 25708557].
Noto H, Goto A, Tsujimoto T, Noda M. Cancer risk in diabetic patients treated with metformin: a systematic review and meta-analysis. PLoS One 2012; 7(3): e33411. []. [PMID: 22448244].
Hwang IC, Park SM, Shin D, Ahn HY, Rieken M, Shariat SF. Metformin association with lower prostate cancer recurrence in type 2 diabetes: a systematic review and meta-analysis. Asian Pac J Cancer Prev 2015; 16(2): 595-600. []. [PMID: 25684493].
Soranna D, Scotti L, Zambon A, et al. Cancer risk associated with use of metformin and sulfonylurea in type 2 diabetes: a meta-analysis. Oncologist 2012; 17(6): 813-22. []. [PMID: 22643536].

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy