Cancer Causes & Control

, Volume 24, Issue 4, pp 769–776 | Cite as

Statin use and risk of bladder cancer: a meta-analysis

  • Xiao-long Zhang
  • Jiang Geng
  • Xiao-peng Zhang
  • Bo Peng
  • Jian-ping Che
  • Yang Yan
  • Guang-chun Wang
  • Sheng-qiang Xia
  • Yan Wu
  • Jun-hua ZhengEmail author
Original paper



Emerging evidence suggests that statins may decrease the risk of cancers. However, available evidence on bladder cancer is conflicting. To quantify the association between statin use and risk of bladder cancer, we performed a detailed meta-analysis of published studies regarding this subject.


A literature search was carried out using MEDLINE, EMBASE, and OVID databases between January 1966 and October 2012. Before meta-analysis, between-study heterogeneity and publication bias were assessed using adequate statistical tests. Fixed- and random-effect models were used to estimate summary relative risks (RR) and the corresponding 95 % confidence intervals (CIs). Potential sources of heterogeneity were detected by meta-regression. Subgroup analyses, sensitivity analysis, and cumulative meta-analysis were also performed.


A total of 13 (three RCTs, five cohort, and five case–control) studies contributed to the analysis. There was heterogeneity among the studies, but no publication bias. Pooled results indicated a nonsignificant increase in total bladder cancer risk among all statin users [RR = 1.07, 95 % CI (0.95, 1.21)]. Long-term statin use did not significantly affect the risk of total bladder cancer [RR = 1.21, 95 % CI (0.92, 1.59)]. In our subgroup analyses, the results were not substantially affected by study design, region, and confounder adjustment. Furthermore, sensitivity analysis confirmed the stability of the results.


The findings of this meta-analysis suggested that there was no association between statin use and risk of bladder cancer. More studies, especially RCTs, are needed to confirm this association.


Statin Bladder cancer Risk Meta-analysis 


Conflict of interest

There are no potential conflicts of interest among all authors.


  1. 1.
    World Health Organization (2011) Cance Stats Cancer worldwide. Available: Accessed 22 Jan 2011
  2. 2.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E et al (2011) Global cancer statistics. CA Cancer J Clin 61:69–90PubMedCrossRefGoogle Scholar
  3. 3.
    National Cancer Institute (2011) SEER stat fact sheets: Bladder. Available: Accessed Jan 22 2011
  4. 4.
    Mills EJ, Rachlis B, Wu P, Devereaux PJ, Arora P et al (2008) Primary prevention of cardiovascular mortality and events with statin treatments: a network meta-analysis involving more than 65,000 patients. J Am Coll Cardiol 52:1769–1781PubMedCrossRefGoogle Scholar
  5. 5.
    Mihaylova B, Emberson J, Blackwell L, Keech A, Simes J et al (2012) The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet 380:581–590PubMedCrossRefGoogle Scholar
  6. 6.
    Newman TB, Hulley SB (1996) Carcinogenicity of lipid-lowering drugs. JAMA 275:55–60PubMedCrossRefGoogle Scholar
  7. 7.
    Keyomarsi K, Sandoval L, Band V, Pardee AB (1991) Synchronization of tumor and normal cells from G1 to multiple cell cycles by lovastatin. Cancer Res 51:3602–3609PubMedGoogle Scholar
  8. 8.
    Wong WW, Dimitroulakos J, Minden MD, Penn LZ (2002) HMG-CoA reductase inhibitors and the malignant cell: the statin family of drugs as triggers of tumor-specific apoptosis. Leukemia 16:508–519PubMedCrossRefGoogle Scholar
  9. 9.
    Dimitroulakos J, Marhin WH, Tokunaga J, Irish J, Gullane P et al (2002) Microarray and biochemical analysis of lovastatin-induced apoptosis of squamous cell carcinomas. Neoplasia 4:337–346PubMedCrossRefGoogle Scholar
  10. 10.
    Park HJ, Kong D, Iruela-Arispe L, Begley U, Tang D et al (2002) 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors interfere with angiogenesis by inhibiting the geranylgeranylation of RhoA. Circ Res 91:143–150PubMedCrossRefGoogle Scholar
  11. 11.
    Weis M, Heeschen C, Glassford AJ, Cooke JP (2002) Statins have biphasic effects on angiogenesis. Circulation 105:739–745PubMedCrossRefGoogle Scholar
  12. 12.
    Alonso DF, Farina HG, Skilton G, Gabri MR, De Lorenzo MS et al (1998) Reduction of mouse mammary tumor formation and metastasis by lovastatin, an inhibitor of the mevalonate pathway of cholesterol synthesis. Breast Cancer Res Treat 50:83–93PubMedCrossRefGoogle Scholar
  13. 13.
    Kusama T, Mukai M, Iwasaki T, Tatsuta M, Matsumoto Y et al (2002) 3-Hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors reduce human pancreatic cancer cell invasion and metastasis. Gastroenterology 122:308–317PubMedCrossRefGoogle Scholar
  14. 14.
    Kamat AM, Nelkin GM (2005) Atorvastatin: a potential chemopreventive agent in bladder cancer. Urology 66:1209–1212PubMedCrossRefGoogle Scholar
  15. 15.
    Clearfield M, Downs JR, Weis S, Whitney EJ, Kruyer W et al (2001) Air Force/Texas coronary atherosclerosis prevention study (AFCAPS/TexCAPS): efficacy and tolerability of long-term treatment with lovastatin in women. J Womens Health Gend Based Med 10:971–981PubMedCrossRefGoogle Scholar
  16. 16.
    Graaf MR, Beiderbeck AB, Egberts AC, Richel DJ, Guchelaar HJ (2004) The risk of cancer in users of statins. J Clin Oncol 22:2388–2394PubMedCrossRefGoogle Scholar
  17. 17.
    Kaye JA, Jick H (2004) Statin use and cancer risk in the General Practice Research Database. Br J Cancer 90:635–637PubMedCrossRefGoogle Scholar
  18. 18.
    Strandberg TE, Pyorala K, Cook TJ, Wilhelmsen L, Faergeman O et al (2004) Mortality and incidence of cancer during 10-year follow-up of the Scandinavian Simvastatin Survival Study (4S). Lancet 364:771–777PubMedCrossRefGoogle Scholar
  19. 19.
    Heart Protection Study Collaborative Group. The effects of cholesterol lowering with simvastatin on cause-specific mortality and on cancer incidence in 20,536 high-risk people: a randomised placebo-controlled trial [ISRCTN48489393]. BMC Med. 2005 Mar 16;3:6Google Scholar
  20. 20.
    Coogan PF, Rosenberg L, Strom BL (2007) Statin use and the risk of 10 cancers. Epidemiology 18:213–219PubMedCrossRefGoogle Scholar
  21. 21.
    Farwell WR, Scranton RE, Lawler EV, Lew RA, Brophy MT et al (2008) The association between statins and cancer incidence in a veterans population. J Natl Cancer Inst 100:134–139PubMedCrossRefGoogle Scholar
  22. 22.
    Haukka J, Sankila R, Klaukka T, Lonnqvist J, Niskanen L et al (2010) Incidence of cancer and statin usage–record linkage study. Int J Cancer 126:279–284PubMedCrossRefGoogle Scholar
  23. 23.
    Jacobs EJ, Newton CC, Thun MJ, Gapstur SM (2011) Long-term use of cholesterol-lowering drugs and cancer incidence in a large United States cohort. Cancer Res 71:1763–1771PubMedCrossRefGoogle Scholar
  24. 24.
    Kuo CC, Chiu HF, Lee IM, Kuo HW, Lee CT et al (2012) Statin use and the risk of bladder cancer: a population-based case-control study. Expert Opin Drug Saf 11:733–738PubMedCrossRefGoogle Scholar
  25. 25.
    Friedman GD, Flick ED, Udaltsova N, Chan J, Quesenberry CP Jr et al (2008) Screening statins for possible carcinogenic risk: up to 9 years of follow-up of 361,859 recipients. Pharmacoepidemiol Drug Saf 17:27–36PubMedCrossRefGoogle Scholar
  26. 26.
    Vinogradova Y, Coupland C, Hippisley-Cox J (2011) Exposure to statins and risk of common cancers: a series of nested case-control studies. BMC Cancer 11:409PubMedCrossRefGoogle Scholar
  27. 27.
    Sato S, Ajiki W, Kobayashi T, Awata N (2006) Pravastatin use and the five-year incidence of cancer in coronary heart disease patients: from the prevention of coronary sclerosis study. J Epidemiol 16:201–206PubMedCrossRefGoogle Scholar
  28. 28.
    Dale KM, Coleman CI, Henyan NN, Kluger J, White CM (2006) Statins and cancer risk: a meta-analysis. JAMA 295:74–80PubMedCrossRefGoogle Scholar
  29. 29.
    Browning DR, Martin RM (2007) Statins and risk of cancer: a systematic review and metaanalysis. Int J Cancer 120:833–843PubMedCrossRefGoogle Scholar
  30. 30.
    Emberson JR, Kearney PM, Blackwell L, Newman C, Reith C et al (2012) Lack of effect of lowering LDL cholesterol on cancer: meta-analysis of individual data from 175,000 people in 27 randomised trials of statin therapy. PLoS ONE 7:e29849PubMedCrossRefGoogle Scholar
  31. 31.
    Kuoppala J, Lamminpaa A, Pukkala E (2008) Statins and cancer: a systematic review and meta-analysis. Eur J Cancer 44:2122–2132PubMedCrossRefGoogle Scholar
  32. 32.
    Moher D, Liberati A, Tetzlaff J, Altman DG (2010) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg 8:336–341PubMedCrossRefGoogle Scholar
  33. 33.
    Higgins JP, Green S (2011) Cochrane handbook for systematic reviews of interventions.
  34. 34.
    Wells GA, Shea B, O’Connell D, Peterson J, Welch V, Losos M, Tugwell P (2012) The Newcastle–Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses.
  35. 35.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560PubMedCrossRefGoogle Scholar
  36. 36.
    Higgins JP, Thompson SG (2004) Controlling the risk of spurious findings from meta-regression. Stat Med 23:1663–1682PubMedCrossRefGoogle Scholar
  37. 37.
    Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634PubMedCrossRefGoogle Scholar
  38. 38.
    Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50:1088–1101PubMedCrossRefGoogle Scholar
  39. 39.
    Rogers MJ (2000) Statins: lower lipids and better bones? Nat Med 6:21–23PubMedCrossRefGoogle Scholar
  40. 40.
    Hamelin BA, Turgeon J (1998) Hydrophilicity/lipophilicity: relevance for the pharmacology and clinical effects of HMG-CoA reductase inhibitors. Trends Pharmacol Sci 19:26–37PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Xiao-long Zhang
    • 1
    • 2
  • Jiang Geng
    • 1
    • 2
  • Xiao-peng Zhang
    • 1
    • 2
  • Bo Peng
    • 1
    • 2
  • Jian-ping Che
    • 1
  • Yang Yan
    • 1
  • Guang-chun Wang
    • 1
  • Sheng-qiang Xia
    • 1
  • Yan Wu
    • 2
  • Jun-hua Zheng
    • 1
    • 2
    Email author
  1. 1.Department of Urology, Shanghai Tenth People’s HospitalTongji UniversityShanghaiPeople’s Republic of China
  2. 2.Department of First Clinical Medical CollegeNanjing Medical UniversityNanjingPeople’s Republic of China

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