Statins and the risk of colorectal cancer: An updated systematic review and meta-analysis of 40 studies

World Journal of Gastroenterology

Volumn 20, Issue 7, 2014, Pages 1858-1870

  Lytras, Theodore ^a   Nikolopoulos, Georgios ^b,c   Bonovas, Stefanos ^d,e  

^a NATIONAL SCHOOL OF PUBLIC HEALTH   (Greece)

^b NATIONAL DEVELOPMENT AND RESEARCH INSTITUTES   (United States)

^c Hellenic Centre for Disease Control and Prevention   (Greece)

^d UNIVERSITY OF ATHENS MEDICAL SCHOOL   (Greece)

^e MARIO NEGRI INSTITUTE FOR PHARMACOLOGICAL RESEARCH   (Italy)

Author keywords

3 hydroxy 3 methylglutaryl coenzyme A reductase inhibitors; Cancer chemoprevention; Colorectal cancer; Meta analysis; Statins; Systematic review

Indexed keywords

HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; MEVINOLIN; PRAVASTATIN; ROSUVASTATIN; SIMVASTATIN;

ARTICLE; CANCER RISK; COHORT ANALYSIS; COLORECTAL CANCER; DISEASE ASSOCIATION; HUMAN; META ANALYSIS; PUBLISHING; RANDOMIZED CONTROLLED TRIAL (TOPIC); SENSITIVITY ANALYSIS; SYSTEMATIC REVIEW; COLORECTAL NEOPLASMS; OBSERVATIONAL STUDY; REPRODUCIBILITY; RISK FACTOR; SENSITIVITY AND SPECIFICITY;

COLORECTAL NEOPLASMS; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; OBSERVATIONAL STUDY AS TOPIC; RANDOMIZED CONTROLLED TRIALS AS TOPIC; REPRODUCIBILITY OF RESULTS; RISK FACTORS; SENSITIVITY AND SPECIFICITY;

EID: 84894265324     PISSN: 10079327     EISSN: 22192840     Source Type: Journal    
DOI: 10.3748/wjg.v20.i7.1858     Document Type: Article

References (98)

1. Walley T, Folino-Gallo P, Schwabe U, van Ganse E. Variations and increase in use of statins across Europe: data from administrative databases. BMJ 2004; 328: 385-386 [PMID: 14962875. DOI: 10.1136/bmj.328.7436.385]
2. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344: 1383-1389 [PMID: 7968073]
3. Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, McKillop JH, Packard CJ. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med 1995; 333: 1301-1307 [PMID: 7566020 DOI: 10.1056/NEJM199511163332001]
4. Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, Brown L, Warnica JW, Arnold JM, Wun CC, Davis BR, Braunwald E. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med 1996; 335: 1001-1009 [PMID: 8801446. DOI: 10.1056/NEJM199610033351401]
5. Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, Langendorfer A, Stein EA, Kruyer W, Gotto AM. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 1998; 279: 1615-1622 [PMID: 9613910]
6. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. N Engl J Med 1998; 339: 1349-1357 [PMID: 9841303 DOI: 10.1056/NEJM199811053391902]
7. Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008; 359: 2195-2207 [PMID: 18997196 DOI: 10.1056/NEJMoa0807646]
8. Goldstein JL, Brown MS. Regulation of the mevalonate pathway. Nature 1990; 343: 425-430 [PMID: 1967820 DOI: 10.1038/343425a0]
9. Witztum JL, Steinberg D. Role of oxidized low density lipoprotein in atherogenesis. J Clin Invest 1991; 88: 1785-1792 [PMID: 1752940 DOI: 10.1172/JCI115499]
10. Gazzerro P, Proto MC, Gangemi G, Malfitano AM, Ciaglia E, Pisanti S, Santoro A, Laezza C, Bifulco M. Pharmacological actions of statins: a critical appraisal in the management of cancer. Pharmacol Rev 2012; 64: 102-146 [PMID: 22106090 DOI: 10.1124/pr.111.004994]
11. Bonetti PO, Lerman LO, Napoli C, Lerman A. Statin effects beyond lipid lowering--are they clinically relevant? Eur Heart J 2003; 24: 225-248 [PMID: 12590901]
12. Davignon J. Beneficial cardiovascular pleiotropic effects of statins. Circulation 2004; 109: III39-III43 [PMID: 15198965 DOI: 10.1161/01.CIR.0000131517.20177.5a]
13. Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, Kirby A, Sourjina T, Peto R, Collins R, Simes R. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 2005; 366: 1267-1278 [PMID: 16214597 DOI: 10.1016/S0140-6736(05)67394-1]
14. Katz MS. Therapy insight: Potential of statins for cancer chemoprevention and therapy. Nat Clin Pract Oncol 2005; 2: 82-89 [PMID: 16264880 DOI: 10.1038/ncponc0097]
15. Demierre MF, Higgins PD, Gruber SB, Hawk E, Lippman SM. Statins and cancer prevention. Nat Rev Cancer 2005; 5: 930-942 [PMID: 16341084 DOI: 10.1038/nrc1751]
16. Hindler K, Cleeland CS, Rivera E, Collard CD. The role of statins in cancer therapy. Oncologist 2006; 11: 306-315 [PMID: 16549815. DOI: 10.1634/theoncologist.11-3-306]
17. Chan KK, Oza AM, Siu LL. The statins as anticancer agents. Clin Cancer Res 2003; 9: 10-19 [PMID: 12538446]
18. Boudreau DM, Yu O, Johnson J. Statin use and cancer risk: a comprehensive review. Expert Opin Drug Saf 2010; 9: 603-621 [PMID: 20377474 DOI: 10.1517/14740331003662620]
19. Bjerre LM, LeLorier J. Do statins cause cancer? A metaanalysis of large randomized clinical trials. Am J Med 2001; 110: 716-723 [PMID: 11403756]
20. Dale KM, Coleman CI, Henyan NN, Kluger J, White CM. Statins and cancer risk: a meta-analysis. JAMA 2006; 295: 74-80 [PMID: 16391219 DOI: 10.1001/jama.295.1.74]
21. Bonovas S, Filioussi K, Tsavaris N, Sitaras NM. Statins and cancer risk: a literature-based meta-analysis and metaregression analysis of 35 randomized controlled trials. J Clin Oncol 2006; 24: 4808-4817 [PMID: 17001070 DOI: 10.1200/ JCO.2006.06.3560]
22. Emberson JR, Kearney PM, Blackwell L, Newman C, Reith C, Bhala N, Holland L, Peto R, Keech A, Collins R, Simes J, Baigent C. 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 2012; 7: e29849 [PMID: 22276132 DOI: 10.1371/journal.pone.0029849]
23. Lochhead P, Chan AT. Statins and colorectal cancer. Clin Gastroenterol Hepatol 2013; 11: 109-118; quiz e13-14 [PMID: 22982096. DOI: 10.1016/j.cgh.2012.08.037]
24. Bonovas S, Tsantes A, Drosos T, Sitaras NM. Cancer chemoprevention: a summary of the current evidence. Anticancer Res 2008; 28: 1857-1866 [PMID: 18630472]
25. Poynter JN, Gruber SB, Higgins PD, Almog R, Bonner JD, Rennert HS, Low M, Greenson JK, Rennert G. Statins and the risk of colorectal cancer. N Engl J Med 2005; 352: 2184-2192 [PMID: 15917383 DOI: 10.1056/NEJMoa043792]
26. Vinogradova Y, Coupland C, Hippisley-Cox J. Exposure to statins and risk of common cancers: a series of nested casecontrol studies. BMC Cancer 2011; 11: 409 [PMID: 21943022 DOI: 10.1186/1471-2407-11-409]
27. Bonovas S, Filioussi K, Flordellis CS, Sitaras NM. Statins and the risk of colorectal cancer: a meta-analysis of 18 studies involving more than 1.5 million patients. J Clin Oncol 2007; 25: 3462-3468 [PMID: 17687150 DOI: 10.1200/JCO.2007.10.8936]
28. Greenland S. Invited commentary: a critical look at some popular meta-analytic methods. Am J Epidemiol 1994; 140: 290-296 [PMID: 8030632]
29. Emerson JD, Burdick E, Hoaglin DC, Mosteller F, Chalmers TC. An empirical study of the possible relation of treatment differences to quality scores in controlled randomized clinical trials. Control Clin Trials 1990; 11: 339-352 [PMID: 1963128]
30. Greenland S. Quantitative methods in the review of epidemiologic literature. Epidemiol Rev 1987; 9: 1-30 [PMID: 3678409]
31. Altman DG, Bland JM. Interaction revisited: the difference between two estimates. BMJ 2003; 326: 219 [PMID: 12543843]
32. Petitti DB. Statistical methods in meta-analysis. In: Petitti DB. Meta-Analysis, Decision Analysis, and Cost-Effectiveness Analysis. New York: Oxford University Press, 1999
33. Team RDC. R: A Language and Environment for Statistical Computing [Internet]. Vienna, Austria: R Foundation for Statistical Computing, 2013. Available from: URL: http:// www.R-project.org/
34. Schwarzer G. Meta: An R package for meta-analysis [Internet]. 2013. Available from: URL: http://cran.r-project.org/ package=meta
35. Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 1959; 22: 719-748 [PMID: 13655060]
36. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177-188 [PMID: 3802833]
37. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics 1994; 50: 1088-1101 [PMID: 7786990]
38. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629-634 [PMID: 9310563]
39. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327: 557-560 [PMID: 12958120 DOI: 10.1136/bmj.327.7414.557]
40. Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions. Chichester: The Cochrane Collaboration, 2008
41. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB. Metaanalysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000; 283: 2008-2012 [PMID: 10789670]
42. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med 2009; 6: e1000100 [PMID: 19621070 DOI: 10.1371/journal. pmed.1000100]
43. Hsia J, MacFadyen JG, Monyak J, Ridker PM. Cardiovascular event reduction and adverse events among subjects attaining low-density lipoprotein cholesterol & lt; 50 mg/dl with rosuvastatin. The JUPITER trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin). J Am Coll Cardiol 2011; 57: 1666-1675 [PMID: 21492764. DOI: 10.1016/j.jacc.2010.09.082]
44. Ford I, Murray H, Packard CJ, Shepherd J, Macfarlane PW, Cobbe SM. Long-term follow-up of the West of Scotland Coronary Prevention Study. N Engl J Med 2007; 357: 1477-1486 [PMID: 17928595 DOI: 10.1056/NEJMoa065994]
45. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebocontrolled trial. Lancet 2002; 360: 7-22 [PMID: 12114036 DOI: 10.1016/S0140-6736(02)09327-3]
46. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT). JAMA 2002; 288: 2998-3007 [PMID: 12479764]
47. Strandberg TE, Pyörälä K, Cook TJ, Wilhelmsen L, Faergeman O, Thorgeirsson G, Pedersen TR, Kjekshus J. Mortality and incidence of cancer during 10-year follow-up of the Scandinavian Simvastatin Survival Study (4S). Lancet 2004; 364: 771-777 [PMID: 15337403 DOI: 10.1016/S0140-6736(04)16936-5]
48. LIPID Study Group (Long-term Intervention with Pravastatin in Ischaemic Disease). Long-term effectiveness and safety of pravastatin in 9014 patients with coronary heart disease and average cholesterol concentrations: the LIPID trial follow-up. Lancet 2002; 359: 1379-1387 [PMID: 11978335 DOI: 10.1016/ S0140-6736(02)08351-4]
49. Leung HW, Chan AL, Lo D, Leung JH, Chen HL. Common cancer risk and statins: a population-based case-control study in a Chinese population. Expert Opin Drug Saf 2013; 12: 19-27 [PMID: 23199231 DOI: 10.1517/14740338.2013.744392]
50. Clancy Z, Keith SW, Rabinowitz C, Ceccarelli M, Gagne JJ, Maio V. Statins and colorectal cancer risk: a longitudinal study. Cancer Causes Control 2013; 24: 777-782 [PMID: 23361340. DOI: 10.1007/s10552-013-0160-x]
51. Simon MS, Rosenberg CA, Rodabough RJ, Greenland P, Ockene I, Roy HK, Lane DS, Cauley JA, Khandekar J. Prospective analysis of association between use of statins or other lipid-lowering agents and colorectal cancer risk. Ann Epidemiol 2012; 22: 17-27 [PMID: 22056480 DOI: 10.1016/ j.annepidem.2011.10.006]
52. Lee JE, Baba Y, Ng K, Giovannucci E, Fuchs CS, Ogino S, Chan AT. Statin use and colorectal cancer risk according to molecular subtypes in two large prospective cohort studies. Cancer Prev Res (Phila) 2011; 4: 1808-1815 [PMID: 21680706 DOI: 10.1158/1940-6207.CAPR-11-0113]
53. Jacobs EJ, Newton CC, Thun MJ, Gapstur SM. Long-term use of cholesterol-lowering drugs and cancer incidence in a large United States cohort. Cancer Res 2011; 71: 1763-1771 [PMID: 21343395 DOI: 10.1158/0008-5472.CAN-10-2953]
54. Matsushita Y, Sugihara M, Kaburagi J, Ozawa M, Iwashita M, Yoshida S, Saito H, Hattori Y. Pravastatin use and cancer risk: a meta-analysis of individual patient data from longterm prospective controlled trials in Japan. Pharmacoepidemiol Drug Saf 2010; 19: 196-202 [PMID: 19856484 DOI: 10.1002/ pds.1870]
55. Haukka J, Sankila R, Klaukka T, Lonnqvist J, Niskanen L, Tanskanen A, Wahlbeck K, Tiihonen J. Incidence of cancer and statin usage--record linkage study. Int J Cancer 2010; 126: 279-284 [PMID: 19739258 DOI: 10.1002/ijc.24536]
56. Singh H, Mahmud SM, Turner D, Xue L, Demers AA, Bernstein CN. Long-term use of statins and risk of colorectal cancer: a population-based study. Am J Gastroenterol 2009; 104: 3015-3023 [PMID: 19809413 DOI: 10.1038/ajg.2009.574]
57. Flick ED, Habel LA, Chan KA, Haque R, Quinn VP, Van Den Eeden SK, Sternfeld B, Orav EJ, Seeger JD, Quesenberry CP, Caan BJ. Statin use and risk of colorectal cancer in a cohort of middle-aged men in the US: a prospective cohort study. Drugs 2009; 69: 1445-1457 [PMID: 19634923 DOI: 10.2165/00003495-200969110-00004]
58. Friedman GD, Flick ED, Udaltsova N, Chan J, Quesenberry CP, Habel LA. Screening statins for possible carcinogenic risk: up to 9 years of follow-up of 361,859 recipients. Pharmacoepidemiol Drug Saf 2008; 17: 27-36 [PMID: 17944002 DOI: 10.1002/pds.1507]
59. Farwell WR, Scranton RE, Lawler EV, Lew RA, Brophy MT, Fiore LD, Gaziano JM. The association between statins and cancer incidence in a veterans population. J Natl Cancer Inst 2008; 100: 134-139 [PMID: 18182618 DOI: 10.1093/jnci/ djm286]
60. Setoguchi S, Glynn RJ, Avorn J, Mogun H, Schneeweiss S. Statins and the risk of lung, breast, and colorectal cancer in the elderly. Circulation 2007; 115: 27-33 [PMID: 17179016 DOI: 10.1161/CIRCULATIONAHA.106.650176]
61. Friis S, Poulsen AH, Johnsen SP, McLaughlin JK, Fryzek JP, Dalton SO, Sørensen HT, Olsen JH. Cancer risk among statin users: a population-based cohort study. Int J Cancer 2005; 114: 643-647 [PMID: 15578694 DOI: 10.1002/ijc.20758]
62. Deshpande G. Association between cardiovascular drugs and colon cancer [Internet]. Cited Aug 13 2013. Available from: URL: http://archive.hshsl.umaryland.edu/handle/10713/2752
63. Lakha F, Theodoratou E, Farrington SM, Tenesa A, Cetnarskyj R, Din FV, Porteous ME, Dunlop MG, Campbell H. Statin use and association with colorectal cancer survival and risk: case control study with prescription data linkage. BMC Cancer 2012; 12: 487 [PMID: 23088590 DOI: 10.1186/147 1-2407-12-487]
64. Broughton T, Sington J, Beales IL. Statin use is associated with a reduced incidence of colorectal cancer: a colonoscopycontrolled case-control study. BMC Gastroenterol 2012; 12: 36 [PMID: 22530742 DOI: 10.1186/1471-230X-12-36]
65. Cheng MH, Chiu HF, Ho SC, Tsai SS, Wu TN, Yang CY. Statin use and the risk of colorectal cancer: a populationbased case-control study. World J Gastroenterol 2011; 17: 5197-5202 [PMID: 22215945 DOI: 10.3748/wjg.v17.i47.5197]
66. Robertson DJ, Riis AH, Friis S, Pedersen L, Baron JA, Sørensen HT. Neither long-term statin use nor atherosclerotic disease is associated with risk of colorectal cancer. Clin Gastroenterol Hepatol 2010; 8: 1056-1061 [PMID: 20816860 DOI: 10.1016/j.cgh.2010.08.010]
67. Shadman M, Newcomb PA, Hampton JM, Wernli KJ, Trentham-Dietz A. Non-steroidal anti-inflammatory drugs and statins in relation to colorectal cancer risk. World J Gastroenterol 2009; 15: 2336-2339 [PMID: 19452574]
68. Hachem C, Morgan R, Johnson M, Kuebeler M, El-Serag H. Statins and the risk of colorectal carcinoma: a nested case-control study in veterans with diabetes. Am J Gastroenterol 2009; 104: 1241-1248 [PMID: 19352344 DOI: 10.1038/ ajg.2009.64]
69. Yang YX, Hennessy S, Propert K, Hwang WT, Sarkar M, Lewis JD. Chronic statin therapy and the risk of colorectal cancer. Pharmacoepidemiol Drug Saf 2008; 17: 869-876 [PMID: 18412290. DOI: 10.1002/pds.1599]
70. Boudreau DM, Koehler E, Rulyak SJ, Haneuse S, Harrison R, Mandelson MT. Cardiovascular medication use and risk for colorectal cancer. Cancer Epidemiol Biomarkers Prev 2008; 17: 3076-3080 [PMID: 18957524 DOI: 10.1158/1055-9965. EPI-08-0095]
71. Hoffmeister M, Chang-Claude J, Brenner H. Individual and joint use of statins and low-dose aspirin and risk of colorectal cancer: a population-based case-control study. Int J Cancer 2007; 121: 1325-1330 [PMID: 17487832 DOI: 10.1002/ ijc.22796]
72. Coogan PF, Smith J, Rosenberg L. Statin use and risk of colorectal cancer. J Natl Cancer Inst 2007; 99: 32-40 [PMID: 17202111. DOI: 10.1093/jnci/djk003]
73. Li L, Thompson C, Tucker T. No association between lipidlowering statin use and risk of colon cancer (abstract CC7). In: Proceedings of the 34th Annual Meeting of the North American Primary Care Research Group (NAPCRG). AZ: Tucson, 2006
74. Rubin DT, Blumentals WA, Sheer RL, Steinbuch M, Law L. Statins and risk of colorectal cancer: Results from a large case-control study. Am J Gastroenterol 2005; 100: S394
75. Khurana V, Jaganmohan S, Chalasani R, Singh T, Roy P, Caldito G, Fort C. Statins do not reduce colon cancer risk in humans: A case-control study in half million veterans. Am J Gastroenterol 2004; 99: S242
76. Kaye JA, Jick H. Statin use and cancer risk in the General Practice Research Database. Br J Cancer 2004; 90: 635-637 [PMID: 14760377 DOI: 10.1038/sj.bjc.6601566]
77. Graaf MR, Beiderbeck AB, Egberts AC, Richel DJ, Guchelaar HJ. The risk of cancer in users of statins. J Clin Oncol 2004; 22: 2388-2394 [PMID: 15197200 DOI: 10.1200/JCO.2004.02.027]
78. Blais L, Desgagné 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 [PMID: 10927735]
79. L'Abbé KA, Detsky AS, O'Rourke K. Meta-analysis in clinical research. Ann Intern Med 1987; 107: 224-233 [PMID: 3300460]
80. Sporn MB. Approaches to prevention of epithelial cancer during the preneoplastic period. Cancer Res 1976; 36: 2699-2702 [PMID: 1277177]
81. Bonovas S. Cancer chemoprevention: progress and perspectives. Curr Drug Targets 2011; 12: 1871-1873 [PMID: 21158713]
82. Bonovas S, Nikolopoulos G, Filioussi K, Peponi E, Bagos P, Sitaras NM. Can statin therapy reduce the risk of melanoma? A meta-analysis of randomized controlled trials. Eur J Epidemiol 2010; 25: 29-35 [PMID: 19844794 DOI: 10.1007/s10654-009-9396-x]
83. Bonovas S, Filioussi K, Sitaras NM. Statins are not associated with a reduced risk of pancreatic cancer at the population level, when taken at low doses for managing hypercholesterolemia: evidence from a meta-analysis of 12 studies. Am J Gastroenterol 2008; 103: 2646-2651 [PMID: 18684187 DOI: 10.1111/j.1572-0241.2008.02051.x]
84. Bonovas S, Filioussi K, Sitaras NM. Statin use and the risk of prostate cancer: A metaanalysis of 6 randomized clinical trials and 13 observational studies. Int J Cancer 2008; 123: 899-904 [PMID: 18491405 DOI: 10.1002/ijc.23550]
85. Bonovas S, Filioussi K, Tsantes A, Sitaras NM. Use of statins and risk of haematological malignancies: a meta-analysis of six randomized clinical trials and eight observational studies. Br J Clin Pharmacol 2007; 64: 255-262 [PMID: 17578480 DOI: 10.1111/j.1365-2125.2007.02959.x]
86. Bonovas S, Filioussi K, Tsavaris N, Sitaras NM. Use of statins and breast cancer: a meta-analysis of seven randomized clinical trials and nine observational studies. J Clin Oncol 2005; 23: 8606-8612 [PMID: 16260694 DOI: 10.1200/ JCO.2005.02.7045]
87. Bonovas S, Sitaras NM. Does pravastatin promote cancer in elderly patients? A meta-analysis. CMAJ 2007; 176: 649-654 [PMID: 17325332 DOI: 10.1503/cmaj.060803]
88. Weverling-Rijnsburger AW, Blauw GJ, Lagaay AM, Knook DL, Meinders AE, Westendorp RG. Total cholesterol and risk of mortality in the oldest old. Lancet 1997; 350: 1119-1123 [PMID: 9343498]
89. Bonovas S, Nikolopoulos G, Sitaras NM. Efficacy and safety of more intensive lowering of LDL cholesterol. Lancet 2011; 377: 715; author reply 715-716 [PMID: 21353894 DOI: 10.1016/ S0140-6736(11)60261-4]
90. Nikolopoulos GK, Bagos PG, Bonovas S. Developing the evidence base for cancer chemoprevention: use of meta-analysis. Curr Drug Targets 2011; 12: 1989-1997 [PMID: 21158703]
91. Jänne PA, Mayer RJ. Chemoprevention of colorectal cancer. N Engl J Med 2000; 342: 1960-1968 [PMID: 10874065 DOI: 10.1056/NEJM200006293422606]
92. Bonovas S, Nikolopoulos GK, Bagos PG. Use of fibrates and cancer risk: a systematic review and meta-analysis of 17 longterm randomized placebo-controlled trials. PLoS One 2012; 7: e45259 [PMID: 23028888 DOI: 10.1371/journal.pone.0045259]
93. Shen L, Toyota M, Kondo Y, Lin E, Zhang L, Guo Y, Hernandez NS, Chen X, Ahmed S, Konishi K, Hamilton SR, Issa JP. Integrated genetic and epigenetic analysis identifies three different subclasses of colon cancer. Proc Natl Acad Sci U S A 2007; 104: 18654-18659 [PMID: 18003927 DOI: 10.1073/ pnas.0704652104]
94. Markowitz SD, Bertagnolli MM. Molecular origins of cancer: Molecular basis of colorectal cancer. N Engl J Med 2009; 361: 2449-2460 [PMID: 20018966 DOI: 10.1056/NEJMra0804588]
95. Lipkin SM, Chao EC, Moreno V, Rozek LS, Rennert H, Pinchev M, Dizon D, Rennert G, Kopelovich L, Gruber SB. Genetic variation in 3-hydroxy-3-methylglutaryl CoA reductase modifies the chemopreventive activity of statins for colorectal cancer. Cancer Prev Res (Phila) 2010; 3: 597-603 [PMID: 20403997 DOI: 10.1158/1940-6207.CAPR-10-0007]
96. Schisterman EF, Cole SR, Platt RW. Overadjustment bias and unnecessary adjustment in epidemiologic studies. Epidemiology 2009; 20: 488-495 [PMID: 19525685 DOI: 10.1097/ EDE.0b013e3181a819a1]
97. Bonovas S, Sitaras NM. Statins and cancer risk: a confounded association. Gastroenterology 2009; 137: 740; author reply 740-741 [PMID: 19563833 DOI: 10.1053/j.gastro.2009.02.088]
98. Ahnen DJ, Byers T. Editorial: Colorectal cancer and statins: reflections from the end of the road. Am J Gastroenterol 2009; 104: 3024-3026 [PMID: 19956119 DOI: 10.1038/ajg.2009.572]