Keywords
Statin; Ovarian cancer; Incidence; Mortality
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.
Conclusion: This study determined that statin use reduced the incidence risk of OC and significantly increased the survival in OC patients.
References
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[37] Borgquist S, Broberg P, Tojjar J, Olsson H. Statin use and breast cancer survival - a Swedish nationwide study. BMC Cancer 2019;19(1):54-. doi: 10.1186/s12885-018-5263-z.
[38] Borgquist S, Bjarnadottir O, Kimbung S, Ahern TP. Statins: a role in breast cancer therapy? J Intern Med 2018;284(4):346-57. doi: 10.1111/joim.12806.
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[44] Goldstein MR, Mascitelli L, Pezzetta F. Statins, Tregs and cancer. Atherosclerosis 2008;196(1):483-4. doi: 10.1016/j.atherosclerosis.2007.09.028.
[45] 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. 2019;19(1):730. doi: 10.1186/s12885-019-5954-0.
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[2] Torre LA, Trabert B, DeSantis CE. Ovarian cancer statistics, 2018. 2018;68(4):284-96. doi: 10.3322/caac.21456.
[3] Delgado-Ortega L, González-Domínguez A, Borrás JM, Oliva-Moreno J, González-Haba E, Menjón S, Pérez P, Vicente D, Cordero L, Jiménez M, Simón S, Hidalgo-Vega Á, Moya-Alarcón C. The economic burden of disease of epithelial ovarian cancer in Spain: the OvarCost study. Eur J Health Econ 2019;20(1):135-47. doi: 10.1007/s10198-018-0986-y.
[4] Reid BM, Permuth JB, Sellers TA. Epidemiology of ovarian cancer: a review. Cancer Biol Med 2017;14(1):9-32. doi: 10.20892/j.issn.2095-3941.2016.0084.
[5] Doubeni CA, Doubeni AR, Myers AE. Diagnosis and Management of Ovarian Cancer. American family physician 2016;93(11):937-44.
[6] Roett MA, Evans P. Ovarian cancer: an overview. American family physician 2009;80(6):609-16.
[7] Modugno F, Edwards RP. Ovarian cancer: prevention, detection, and treatment of the disease and its recurrence. Molecular mechanisms and personalized medicine meeting report. Int J Gynecol Cancer 2012;22(8):S45-S57. doi: 10.1097/IGC.0b013e31826bd1f2.
[8] Jawaid S, Gertz M, Corsino C, Cheung J, Seidle H, Couch RD. Human hydroxymethylglutaryl-coenzyme A reductase (HMGCR) and statin sensitivity. Indian journal of biochemistry & biophysics 2010;47(6):331-9.
[9] Davies JT, Delfino SF, Feinberg CE, Johnson MF, Nappi VL, Olinger JT, Schwab AP, Swanson HI. Current and Emerging Uses of Statins in Clinical Therapeutics: A Review. Lipid Insights 2016;9:13-29. doi: 10.4137/LPI.S37450.
[10] Ramkumar S, Raghunath A, Raghunath S. Statin Therapy: Review of Safety and Potential Side Effects. Acta Cardiol Sin 2016;32(6):631-9. doi: 10.6515/ACS20160611A.
[11] Lavie O, Pinchev M, Rennert HS, Segev Y, Rennert G. The effect of statins on risk and survival of gynecological malignancies. Gynecol Oncol 2013;130(3):615-9. doi: 10.1016/j.ygyno.2013.05.025.
[12] Akinwunmi B, Vitonis AF, Titus L, Terry KL, Cramer DW. Statin therapy and association with ovarian cancer risk in the New England Case Control (NEC) study. Int J Cancer 2019;144(5):991-1000. doi: 10.1002/ijc.31758.
[13] Couttenier A, Lacroix O, Vaes E, Cardwell CR, De Schutter H, Robert A. Statin use is associated with improved survival in ovarian cancer: A retrospective population-based study. PLoS One 2017;12(12):e0189233. doi: 10.1371/journal.pone.0189233.
[14] Vogel TJ, Goodman MT, Li AJ, Jeon CY. Statin treatment is associated with survival in a nationally representative population of elderly women with epithelial ovarian cancer. Gynecol Oncol 2017;146(2):340-5. doi: 10.1016/j.ygyno.2017.05.009.
[15] Elmore RG, Ioffe Y, Scoles DR, Karlan BY, Li AJ. Impact of statin therapy on survival in epithelial ovarian cancer. Gynecol Oncol 2008;111(1):102-5.
[16] Urpilainen E, Marttila M, Hautakoski A, Arffman M, Sund R, Ilanne-Parikka P, Arima R, Kangaskokko J, Puistola U, Laara E, Hinkula M. The role of metformin and statins in the incidence of epithelial ovarian cancer in type 2 diabetes: a cohort and nested case-control study. Bjog 2018;125(8):1001-8. doi: 10.1111/1471-0528.15151.
[17] Kabat GC, Kim MY, Chlebowski RT, Vitolins MZ, Wassertheil-Smoller S, Rohan TE. Serum lipids and risk of obesity-related cancers in postmenopausal women. Cancer Causes Control 2018;29(1):13-24. doi: 10.1007/s10552-017-0991-y.
[18] Kaye JA, Jick H. Statin use and cancer risk in the General Practice Research Database. British journal of cancer 2004;90(3):635-7. doi: 10.1038/sj.bjc.6601566.
[19] Verdoodt F, Kjaer Hansen M, Kjaer SK, Pottegard A, Friis S, Dehlendorff C. Statin use and mortality among ovarian cancer patients: A population-based cohort study. International journal of cancer 2017;141(2):279-86. doi: 10.1002/ijc.30738.
[20] Bar D, Lavie O, Stein N, Feferkorn I, Shai A. The effect of metabolic comorbidities and commonly used drugs on the prognosis of patients with ovarian cancer. Eur J Obstet Gynecol Reprod Biol 2016;207:227-31. doi: 10.1016/j.ejogrb.2016.09.005.
[21] Chen HY, Wang Q, Xu QH, Yan L, Gao XF, Lu YH, Wang L. Statin as a Combined Therapy for Advanced-Stage Ovarian Cancer: A Propensity Score Matched Analysis. Biomed Res Int 2016;2016:9125238. doi: 10.1155/2016/9125238.
[22] Desai P, Wallace R, Anderson ML, Howard BV, Ray RM, Wu C, Safford M, Martin LW, Rohan T, Manson JE, Simon MS. 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(3):540-6. doi: 10.1016/j.ygyno.2018.01.006.
[23] Clearfield M, Downs JR, Weis S, Whitney EJ, Kruyer W, Shapiro DR, Stein EA, Langendorfer A, Beere PA, Gotto AM. Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS): efficacy and tolerability of long-term treatment with lovastatin in women. Journal of women's health & gender-based medicine 2001;10(10):971-81. doi: 10.1089/152460901317193549.
[24] Li X, Zhou J. Impact of postdiagnostic statin use on ovarian cancer mortality: A systematic review and meta-analysis of observational studies. British journal of clinical pharmacology 2018;84(6):1109-20. doi: 10.1111/bcp.13559.
[25] Liu Y, Qin A, Li T, Qin X, Li S. Effect of statin on risk of gynecologic cancers: a meta-analysis of observational studies and randomized controlled trials. Gynecologic oncology 2014;133(3):647-55. doi: 10.1016/j.ygyno.2014.04.007.
[26] Lo CK-L, Mertz D, Loeb M. Newcastle-Ottawa Scale: comparing reviewers' to authors' assessments. BMC Med Res Methodol 2014;14:45-. doi: 10.1186/1471-2288-14-45.
[27] Kjaergard LL, Villumsen J, Gluud C. Reported methodologic quality and discrepancies between large and small randomized trials in meta-analyses. Annals of internal medicine 2001;135(11):982-9. doi: 10.7326/0003-4819-135-11-200112040-00010.
[28] Laird NM, Mosteller F. Some statistical methods for combining experimental results. International journal of technology assessment in health care 1990;6(1):5-30.
[29] Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. Bmj 2003;327(7414):557-60.
[30] Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. Bmj 1997;315(7109):629-34.
[31] Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics 1994:1088-101.
[32] Baandrup L, Dehlendorff C, Friis S, Olsen JH, Kjaer SK. Statin use and risk for ovarian cancer: a Danish nationwide case-control study. British journal of cancer 2015;112(1):157-61. doi: 10.1038/bjc.2014.574.
[33] Friedman GD, Flick ED, Udaltsova N, Chan J, Quesenberry CP, Jr., Habel LA. Screening statins for possible carcinogenic risk: up to 9 years of follow-up of 361,859 recipients. Pharmacoepidemiol Drug Saf 2008;17(1):27-36. doi: 10.1002/pds.1507.
[34] Yu O, Boudreau DM, Buist DS, Miglioretti DL. Statin use and female reproductive organ cancer risk in a large population-based setting. Cancer Causes Control 2009;20(5):609-16. doi: 10.1007/s10552-008-9271-1.
[35] Habis M, Wroblewski K, Bradaric M, Ismail N, Yamada SD, Litchfield L, Lengyel E, Romero IL. Statin therapy is associated with improved survival in patients with non-serous-papillary epithelial ovarian cancer: a retrospective cohort analysis. PLoS One 2014;9(8):e104521. doi: 10.1371/journal.pone.0104521.
[36] Harding BN, Delaney JA, Urban RR, Weiss NS. Use of statin medications following diagnosis in relation to survival among women with ovarian cancer. Cancer Epidemiol Biomarkers Prev 2019. doi: 10.1158/1055-9965.epi-18-1194.
[37] Borgquist S, Broberg P, Tojjar J, Olsson H. Statin use and breast cancer survival - a Swedish nationwide study. BMC Cancer 2019;19(1):54-. doi: 10.1186/s12885-018-5263-z.
[38] Borgquist S, Bjarnadottir O, Kimbung S, Ahern TP. Statins: a role in breast cancer therapy? J Intern Med 2018;284(4):346-57. doi: 10.1111/joim.12806.
[39] Beckwitt CH, Shiraha K, Wells A. Lipophilic statins limit cancer cell growth and survival, via involvement of Akt signaling. PloS one 2018;13(5):e0197422-e. doi: 10.1371/journal.pone.0197422.
[40] Borgquist S, Bjarnadottir O, Kimbung S, Ahern TP. Statins: a role in breast cancer therapy? J Intern Med 2018;284(4):346-57. doi: 10.1111/joim.12806.
[41] Stryjkowska-Góra A, Karczmarek-Borowska B, Góra T, Krawczak K. Statins and cancers. Contemp Oncol (Pozn) 2015;19(3):167-75. doi: 10.5114/wo.2014.44294.
[42] Matusewicz L, Meissner J, Toporkiewicz M, Sikorski AF. The effect of statins on cancer cells--review. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 2015;36(7):4889-904. doi: 10.1007/s13277-015-3551-7.
[43] Baandrup L, Dehlendorff C, Friis S, Olsen JH, Kjær SK. Statin use and risk for ovarian cancer: A Danish nationwide case-control study. British Journal of Cancer 2015;112(1):157-61. doi: 10.1038/bjc.2014.574.
[44] Goldstein MR, Mascitelli L, Pezzetta F. Statins, Tregs and cancer. Atherosclerosis 2008;196(1):483-4. doi: 10.1016/j.atherosclerosis.2007.09.028.
[45] 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. 2019;19(1):730. doi: 10.1186/s12885-019-5954-0.
46] Gbelcová H, Rimpelová S, Ruml T, Fenclová M, Kosek V, Hajšlová J, Strnad H, Kolář M, Vítek L. Variability in statin-induced changes in gene expression profiles of pancreatic cancer. Sci Rep 2017;7:44219.
[47] Gitsels LA, Kulinskaya E, Steel N. Survival Benefits of Statins for Primary Prevention: A Cohort Study. PloS one 2016;11(11):e0166847. doi: 10.1371/journal.pone.0166847.
[48] Wu QJ, Tu C, Li YY, Zhu J, Qian KQ, Li WJ, Wu L. Statin use and breast cancer survival and risk: a systematic review and meta-analysis. Oncotarget 2015;6(40):42988-3004. doi: 10.18632/oncotarget.5557.
[49] Zhong S, Zhang X, Chen L, Ma T, Tang J, Zhao J. Statin use and mortality in cancer patients: Systematic review and meta-analysis of observational studies. Cancer treatment reviews 2015;41(6):554-67. doi: 10.1016/j.ctrv.2015.04.005.
[50] Li J, Liu R, Sun Z, Tang S, Wang L, Liu C, Zhao W, Yao Y, Sun C. The association between statin use and endometrial cancer survival outcome: A meta-analysis. Medicine 2018;97(47):e13264. doi: 10.1097/md.0000000000013264.
[51] Chen Y, Li X, Zhang R, Xia Y, Shao Z, Mei Z. Effects of statin exposure and lung cancer survival: A meta-analysis of observational studies. Pharmacological research 2019;141:357-65. doi: 10.1016/j.phrs.2019.01.016.
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