The American Journal of Medicine
Volume 121, Issue 4 , Pages 302-309 , April 2008

Statins and Cancer Risk

  • Igor Karp, MD, MPH, PhD

      Affiliations

    • Department of Social and Preventive Medicine, University of Montreal, Quebec, Canada
    • Population Health Axis, Research Centre, Centre Hospitalier de l’Université de Montréal, Quebec, Canada
    • Division of Clinical Epidemiology, The Research Institute of the McGill University Health Centre, Montreal General Hospita, Quebec, Canada
  • ,
  • Hassan Behlouli, PhD

      Affiliations

    • Division of Clinical Epidemiology, The Research Institute of the McGill University Health Centre, Montreal General Hospita, Quebec, Canada
  • ,
  • Jacques LeLorier, MD, PhD

      Affiliations

    • Pharmacoepidemiology and Pharmacoeconomics Unit, Research Center, Centre Hospitalier de l’Université de Montréal, Quebec, Canada
  • ,
  • Louise Pilote, MD, MPH, PhD

      Affiliations

    • Division of Clinical Epidemiology, The Research Institute of the McGill University Health Centre, Montreal General Hospita, Quebec, Canada
    • Department of Medicine, McGill University, Quebec, Canada
    • Division of Internal Medicine, McGill University, Montreal, Quebec, Canada.
    • Corresponding Author InformationRequests for reprints should be addressed to Louise Pilote, MD, MPH, PhD, Division of Clinical Epidemiology, Royal Victoria Hospital, 687 Pine Avenue West, V Building, Room 2.17, Montreal, Quebec, H3A 1A1.

References 

  1. McKenney JM. Potential nontraditional applications of statins. Ann Pharmacother. 2003;37:1067–1071
  2. Newman T, Hulley S. Carcinogenicity of lipid-lowering drugs. JAMA. 1996;275:55–60
  3. Bjerre LM, LeLorier J. Do statins cause cancer? (A meta-analysis of large randomized clinical trials). Am J Med. 2001;110:716–723
  4. Bonovas S, Filioussi K, Tsavaris N, et al. Statins and cancer risk: a literature-based meta-analysis and meta-regression analysis of 35 randomized controlled trials. J Clin Oncol. 2006;24:4808–4817
  5. Dale KM, Coleman CI, Henyan NN, et al. Statins and cancer risk: a meta-analysis. JAMA. 2006;295:74–80
  6. Demierre MD, Higgins PDR, Gruber SB, et al. Statins and cancer prevention. Nat Rev Cancer. 2005;5:930–942
  7. Friis S, Olsen JH. Statin use and cancer risk: an epidemiologic review. Cancer Invest. 2006;24:413–424
  8. Dimitroulakos J, Ye J, Benzaquen M, et al. Differential sensitivity of various pediatric cancers and squamous cell carcinomas to lovastatin-induced apoptosis: therapeutic implications. Clin Cancer Res. 2001;7:158–167
  9. Frick M, Dulak J, Cisowski J, et al. Statins differentially regulate vascular endothelial growth factor synthesis in endothelial and vascular smooth muscle cells. Atherosclerosis. 2003;170:229–236
  10. Muck AO, Seeger H, Wallwiener D. Class-specific pro-apoptotic effect of statins on human vascular endothelial cells. Z Kardiol. 2004;93:398–402
  11. Urbich C, Dernbach E, Zeiher AM, et al. Double-edged role of statins in angiogenesis signaling. Circ Res. 2002;90:737–744
  12. Weis M, Heeschen C, Glassford AJ, et al. Statins have biphasic effects on angiogenesis. Circulation. 2002;105:739–745
  13. Hawk E, Viner JLV. Statins and cancer—beyond the “one drug, one disease” model. N Engl J Med. 2005;352:2238–2239
  14. Kumar AS, Benz CC, Esserman LJ. [Letter] Clinical trials are required to prove the chemopreventive worth of statins. Arch Intern Med. 2006;166:1143
  15. Duncan RE, El-Sohemy A, Archer MC. Mevalonate promotes the growth of tumors derived from human cancer cells in vivo and stimulates proliferation in vitro with enhanced cyclin-dependent kinase-2 activity. J Biol Chem. 2004;279:33079–33084
  16. Prowell TM, Stearns V, Trock B. Lipophilic statins merit additional study for breast cancer chemoprevention. J Clin Oncol. 2006;24:2128–2129
  17. Sprague J, Wood M. Breast cancer prevention: time for randomized controlled trials with statins. Arch Intern Med. 2006;166:1143–1144
  18. International Classification of Diseases, Clinical Modification, 9th Revision (ICD-9-CM). Washington, DC: Public Health Service, US Department of Health and Human Services; 1998;
  19. Kennedy CC, Brien SE, Tu JV. An overview of the methods and data in the CCORT Canadian Cardiovascular Atlas project. Can J Cardiol. 2003;19:655–663
  20. Zhou Z, Rahme E, Abrahamowicz M, Pilote L. Surival bias associated with time-to-treatment association in drug effectiveness evaluation: a comparison of methods. Am J Epidemiol. 2005;162:1016–1023
  21. Hamelin BA, Turgeon J. Hydrophilicity/lipophilicity: relevance for the pharmacology and clinical effects of HMG-CoA reductase inhibitors. TiPs. 1998;19:26–37
  22. Schachter M. Chemical, pharmacologic and pharmacodynamic properties of statins: an update. Fundam Clin Pharmacol. 2005;19:1897–1898
  23. Duncan RE, El-Sohemy A, Archer MC. Statins and cancer development. Cancer Epidemiol Biomarkers Prev. 2005;14:1897–1898
  24. Stamm JA, Ornstein DL. The role of statins in cancer prevention and treatment. Oncology. 2005;19:739–750
  25. Ghali WA, Quan H, Brant R, et al. Comparison of 2 methods for calculating adjusted survival curves from proportional hazards models. JAMA. 2001;286:1494–1497
  26. Blais L, Desgagne A, Lelorier J. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and the risk of cancer: a nested case-control study. Arch Intern Med. 2000;160:2363–2368
  27. Cauley JA, McTiernan A, Rodabough RJ, et al. Statin use and breast cancer: prospective results from the Women’s Health Initiative. J Natl Cancer Inst. 2006;98:700–707
  28. Friis S, Poulsen AH, Johnsen SP, et al. Cancer risk among statin users: a population-based cohort study. Int J Cancer. 2005;643–647
  29. Setoguchi S, Glynn RJ, Avorn J, et al. Statins and the risk of lung, breast, and colorectal cancer in the elderly. Circulation. 2007;115:27–33
  30. Chan KKW, Oza AM, Siu LL. The statins as anticancer agents. Clin Cancer Res. 2003;9:10–19
  31. Kaushal V, Kohli M, Mehta P, et al. Potential anticancer effects of statins: facts or fiction?. Endothelium. 2003;10:49–58
  32. Sleijfer S, van der Gaast A, Planting AST, et al. The potential of statins as part of anti-cancer treatment. Eur J Cancer. 2005;41:516–522
  33. Platz E, Leitzmann MF, Visvanathan K, et al. Statin drugs and risk of advanced cancer. J Natl Cancer Inst. 2006;98:1819–1825
  34. Duncan RE, El-Sohemy A, Archer MC. Statins and the risk of cancer. [Letter] JAMA. 2006;21:2720
  35. Graaf MR, Beiderbeck AB, Egbergts AC, et al. The risk of cancer in users of statins. J Clin Oncol. 2004;22:2388–2394
  36. Kaye JA, Jick H. Statin use and cancer risk in the General Practice Research Database. Br J Cancer. 2004;90:635–637
  37. Kaye J, Meier CR, Walker AM, et al. Statin use, hyperlipidaimia, and the risk of breast cancer. Br J Cancer. 2002;86:1436–1439
  38. Poynter JN, Gruber SB, Higgins PDR, et al. Statins and the risk of colorectal cancer. N Engl J Med. 2005;352:2184–2192
  39. Zhang Y, Holford TR, Leaderer B, et al. Prior medical conditions and medication use and risk of non-Hodgkin lymphoma in Connecticut United States women. Cancer Causes Control. 2004;15:419–428
  40. Shannon J, Tewoderos S, Garzotto M, et al. Statins and prostate cancer risk: a case-control study. Am J Epidemiol. 2005;162:318–325

 This study was undertaken as part of the Gender and Sex Determinants of Cardiovascular Disease (GENESIS) project, funded by the Canadian Institutes of Health Research Institutes of Gender and Health and Circulatory and Respiratory Health, and Heart and Stroke Foundation of Canada. Dr Pilote is a research scholar of the Canadian Institutes of Health Research and a William Dawson Professor at McGill University. None of the authors have financial interest or conflict with regard to the content discussed in this manuscript. Dr Pilote had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

PII: S0002-9343(08)00074-0

doi: 10.1016/j.amjmed.2007.12.011

The American Journal of Medicine
Volume 121, Issue 4 , Pages 302-309 , April 2008