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Vol. 76, No. 1, 2007
Issue release date: October 2007
Section title: Paper
Digestion 2007;76:51–67
(DOI:10.1159/000108394)

Chemoprevention of Colorectal Cancer

Das D. · Arber N. · Jankowski J.A.
aDigestive Diseases Centre, University Hospitals of Leicester, Leicester, and bDepartment of Clinical Pharmacology, Radcliffe Infirmary, Oxford University, Oxford, UK; cIntegrated Cancer Prevention Centre, Tel Aviv Sourasky Medical Centre and Tel Aviv University, Tel Aviv, Israel

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Article / Publication Details

First-Page Preview
Abstract of Paper

Published online: 10/19/2007

Number of Print Pages: 17
Number of Figures: 1
Number of Tables: 1

ISSN: 0012-2823 (Print)
eISSN: 1421-9867 (Online)

For additional information: http://www.karger.com/DIG

Abstract

Colorectal cancer is a major cause of mortality and treatment costs are considerable. Advocating lifestyle modification, faecal occult blood testing and surveillance colonoscopy in appropriate populations are already in practice. A developing concept is chemoprevention. Several models of carcinogenesis in colorectal cancer have been developed and there is an increasing database on the major molecular mechanisms involved in carcinogenesis mainly from preclinical experiments and phase I trials. There have been several large epidemiological and observational studies to evaluate possible protective effects of >200 agents. More recently, case-control and cohort studies and well-conceived, phase II/III clinical trials have been done or are under way to evaluate putative chemopreventive agents including established drugs like aspirin and non-steroidal anti-inflammatory drugs (NSAIDs), 5-aminosalicylates and statins; more controversial drugs like cyclo-oxygenase-2 (COX-2) inhibitors, ursodeoxycholic acid; various vitamins and micronutrients including calcium, selenium, folic acid, and dietary fibre, fat and protein content. Despite promising outcome in preclinical studies, there is currently very limited data from well-controlled and appropriately powered clinical studies. The most promising agents currently are aspirin, traditional NSAIDs and COX-2 inhibitors. The recent reports of cardiovascular risks of the COX-2 inhibitors and some traditional NSAIDs have resulted in stagnation of the field. Pending the expected release of results from several phase III trials in the near future, chemoprevention for colorectal cancer can only be practically considered in the very-high-risk population like those with familial adenomatous polyposis and ulcerative colitis, in conjunction with surveillance colonoscopy. This article reviews the major models of colorectal carcinogenesis, the concept of chemoprevention with special reference to colorectal cancer and the current state of clinical literature and the future direction of colorectal cancer chemoprevention for both researcher and clinician alike.


Article / Publication Details

First-Page Preview
Abstract of Paper

Published online: 10/19/2007

Number of Print Pages: 17
Number of Figures: 1
Number of Tables: 1

ISSN: 0012-2823 (Print)
eISSN: 1421-9867 (Online)

For additional information: http://www.karger.com/DIG


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Sporn MB: Approaches to prevention of epithelial cancer during the preneoplastic period. Cancer Res 1976;36:2699–2702.
  2. Fearon ER, Vogelstein B: A genetic model for colorectal tumorigenesis. Cell 1990;61:759–767.
  3. Rowan A, Halford S, Gaasenbeek M, Kemp Z, Sieber O, Volikos E, Douglas E, Fiegler H, Carter N, Talbot I, Silver A, Tomlinson I: Refining molecular analysis in the pathways of colorectal carcinogenesis. Clin Gastroenterol Hepatol 2005;3:1115–1123.
  4. Itzkowitz S: Colon carcinogenesis in inflammatory bowel disease: applying molecular genetics to clinical practice. J Clin Gastroenterol 2003;36(suppl 5):S70–S74.

    External Resources

  5. Grady WM, Markowitz S: Genomic instability and colorectal cancer. Curr Opin Gastroenterol 2000;16:62–67.
  6. Itzkowitz SH, Yio X: Inflammation and cancer IV – Colorectal cancer in inflammatory bowel disease: the role of inflammation. Am J Physiol Gastrointest Liver Physiol 2004;287:G7–G17.
  7. Lotan R: Are we ready to use surrogate end points and surrogate tissue to evaluate response to chemopreventive and therapeutic intervention? Clin Cancer Res 2000;6:2126–2128.
  8. Jankowski JA, Hawk ET: A methodological analysis of chemoprevention and cancer prevention strategies for gastrointestinal cancer. Nat Clin Pract Gastroenterol Hepatol 2006;3:1–11.

    External Resources

  9. Bedi A, Pasricha PJ, Akhtar AJ, Barber JP, Bedi GC, Giardiello FM, Zehnbauer BA, Hamilton SR, Jones RJ: Inhibition of apoptosis during development of colorectal cancer. Cancer Res 1995;55:1811–1816.
  10. Chan TA: Nonsteroidal anti-inflammatory drugs, apoptosis, and colon-cancer chemoprevention. Lancet Oncol 2002;3:166–174.
  11. Giovannucci E, Egan KM, Hunter DJ, Stampfer MJ, Colditz GA, Willett WC, Speizer FE: Aspirin and the risk of colorectal cancer in women. N Engl J Med 1995;333:609–614.
  12. Janne PA, Mayer RJ: Chemoprevention of colorectal cancer. N Engl J Med 2000;342:1960–1968.
  13. Giovannucci E, Rimm EB, Stampfer MJ, Colditz GA, Ascherio A, Willett WC: Aspirin use and the risk for colorectal cancer and adenoma in male health professionals. Ann Intern Med 1994;121:241–246.
  14. Cook NR, Lee IM, Gaziano JM, Gordon D, Ridker PM, Manson JE, Hennekens CH, Buring JE: Low-dose aspirin in the primary prevention of cancer – the Women’s Health Study: a randomized controlled trial. JAMA 2005;294:47–55.
  15. Gann PH, Manson JE, Glynn RJ, Buring JE, Hennekens CH: Low-dose aspirin and incidence of colorectal tumors in a randomized trial. J Natl Cancer Inst 1993;85:1220–1224.
  16. Sturmer T, Glynn RJ, Lee IM, Manson JE, Buring JE, Hennekens CH: Aspirin use and colorectal cancer: post-trial follow-up data from the Physicians’ Health Study. Ann Intern Med 1998;28:713–720.
  17. Sandler RS, Halabi S, Baron JA, Budinger S, Paskett E, Keresztes R, Petrelli N, Pipas JM, Karp DD, Loprinzi CL, Steinbach G, Schilsky R: A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. N Engl J Med 2003;348:883–890.
  18. Baron JA, Cole BF, Sandler RS, Haile RW, Ahnen D, Bresalier R, McKeown-Eyssen G, Summers RW, Rothstein R, Burke CA, Snover DC, Church TR, Allen JI, Beach M, Beck GJ, Bond JH, Byers T, Greenberg ER, Mandel JS, Marcon N, Mott LA, Pearson L, Saibil F, van Stolk RU: A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med 2003;348:891–899.
  19. Benamouzig R, Deyra J, Martin A, Girard B, Jullian E, Piednoir B, Couturier D, Coste T, Little J, Chaussade S: Daily soluble aspirin and prevention of colorectal adenoma recurrence: one-year results of the APACC trial. Gastroenterology 2003;125:328–336.
  20. Imperiale TF: Aspirin and the prevention of colorectal cancer. N Engl J Med 2003;348:879–880.
  21. Gridley G, McLaughlin JK, Ekbom A, Klareskog L, Adami HO, Hacker DG, Hoover R, Fraumeni JF Jr: Incidence of cancer among patients with rheumatoid arthritis. J Natl Cancer Inst 1993;85:307–311.
  22. Labayle D, Fischer D, Vielh P, Drouhin F, Pariente A, Bories C, Duhamel O, Trousset M, Attali P: Sulindac causes regression of rectal polyps in familial adenomatous polyposis. Gastroenterology1991;101:635–639.
  23. Giardiello FM, Hamilton SR, Krush AJ, Piantadosi S, Hylind LM, Celano P, Booker SV, Robinson CR, Offerhaus GJ: Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. N Engl J Med 1993;328:1313–1316.
  24. Kargman SL, O’Neill GP, Vickers PJ, Evans JF, Mancini JA, Jothy S: Expression of prostaglandin G/H synthase-1 and -2 in human colon cancer. Cancer Res 1995;55:2556.
  25. Steinbach G, Lynch PM, Phillips RK, Wallace MH, Hawk E, Gordon GB, Wakabayashi N, Saunders B, Shen Y, Fujimura T, Su LK, Levin B: The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med 2000;342:1946–1952.
  26. Arber N, Eagle CJ, Spicak J, Rácz I, Dite P, Hajer J, Zavoral M, Lechuga MJ, Gerletti P, Tang J, Rosenstein RB, Macdonald K, Bhadra P, Fowler R, Wittes J, Zauber AG, Solomon SD, Levin B; PreSAP Trial Investigators: Celecoxib for the prevention of colorectal adenomatous polyps. N Engl J Med 2006;355:885–895.
  27. Bertagnolli MM, Eagle CJ, Zauber AG, Redston M, Solomon SD, Kim K, Tang J, Rosenstein RB, Wittes J, Corle D, Hess TM, Woloj GM, Boisserie F, Anderson WF, Viner JL, Bagheri D, Burn J, Chung DC, Dewar T, Foley TR, Hoffman N, Macrae F, Pruitt RE, Saltzman JR, Salzberg B, Sylwestrowicz T, Gordon GB, Hawk ET; APC Study Investigators: Celecoxib for the prevention of sporadic colorectal adenomas. N Engl J Med 2006;355:873–884.
  28. Kerr DJ, Dunn JA, Langman MJ, Smith JL, Midgley RSJ, Stanley A, Stokes JC, Julier P, Iveson C, Duvvuri R, McConkey CC; VICTOR Trial Group: Rofecoxib and cardiovascular adverse events in adjuvant treatment of colorectal cancer. N Engl J Med 2007;357:360–369.
  29. Solomon SD, McMurray JJ, Pfeffer MA, Wittes J, Fowler R, Finn P, Anderson WF, Zauber A, Hawk E, Bertagnolli M; Adenoma Prevention with Celecoxib (APC) Study Investigators: Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med 2005;352:1071–1080.
  30. Ladabaum U, Scheiman JM, Fendrick AM: Potential effect of cyclooxygenase-2-specific inhibitors on the prevention of colorectal cancer: a cost-effectiveness analysis. Am J Med 2003;114:546–554.
  31. Arguedas MR, Heudebert GR, Wilcox CM: Surveillance colonoscopy or chemoprevention with COX-2 inhibitors in average-risk post-polypectomy patients: a decision analysis. Aliment Pharmacol Ther 2001;15:631–638.
  32. Dommels YE, Haring MM, Keestra NG, Alink GM, van Bladeren PJ, van Ommen B: The role of cyclooxygenase in n-6 and n-3 polyunsaturated fatty acid mediated effects on cell proliferation, PGE(2) synthesis and cytotoxicity in human colorectal carcinoma cell lines. Carcinogenesis 2003;24:385–392.
  33. Reddy S, Rishi AK, Xu H, Levi E, Sarkar FH, Majumdar AP: Mechanisms of curcumin and EGF-receptor related protein (ERRP)-dependent growth inhibition of colon cancer cells. Nutr Cancer 2006;55:185–194.
  34. Kato T, Hancock RL, Mohammadpour H, McGregor B, Manalo P, Khaiboullina S, Hall MR, Pardini L, Pardini RS: Influence of omega-3 fatty acids on the growth of human colon carcinoma in nude mice. Cancer Lett 2002;187:169–177.
  35. Kashfi K, Ryan Y, Qiao LL, Williams JL, Chen J, Del Soldato P, Traganos F, Rigas B, Ryann Y: Nitric oxide-donating nonsteroidal anti-inflammatory drugs inhibit the growth of various cultured human cancer cells: evidence of a tissue type-independent effect. J Pharmacol Exp Ther 2002;303:1273–1282.
  36. Velayos FS, Loftus EV Jr, Jess T, Harmsen WS, Bida J, Zinsmeister AR, Tremaine WJ, Sandborn WJ: Predictive and protective factors associated with colorectal cancer in ulcerative colitis: a case-control study. Gastroenterology 2006;130:1941–1949.
  37. Moody GA, Jayanthi V, Probert CS, Mac Kay H, Mayberry JF: Long-term therapy with sulphasalazine protects against colorectal cancer in ulcerative colitis: a retrospective study of colorectal cancer risk and compliance with treatment in Leicestershire. Eur J Gastroenterol Hepatol 1996;8:1179–1183.
  38. Eaden J, Abrams K, Ekbom A, Jackson E, Mayberry J: Colorectal cancer prevention in ulcerative colitis: a case-control study. Aliment Pharmacol Ther 2000;14:145–153.
  39. Rubin DT, LoSavio A, Yadron N, Huo D, Hanauer SB: Aminosalicylate therapy in the prevention of dysplasia and colorectal cancer in ulcerative colitis. Clin Gastroenterol Hepatol 2006;4:1346–1350.
  40. Jess T, Loftus EV Jr, Velayos FS, Winther KV, Tremaine WJ, Zinsmeister AR, Scott Harmsen W, Langholz E, Binder V, Munkholm P, Sandborn WJ: Risk factors for colorectal neoplasia in inflammatory bowel disease: a nested case-control study from Copenhagen county, Denmark and Olmsted county, Minnesota. Am J Gastroenterol 2007;102:829–836.
  41. Terdiman JP, Steinbuch M, Blumentals WA, Ullman TA, Rubin DT: 5-aminosalicylic acid therapy and the risk of colorectal cancer among patients with inflammatory bowel disease. Inflamm Bowel Dis 2007;13:367–371.
  42. Reinacher-Schick A, Schoeneck A, Graeven U, Schwarte-Waldhoff I, Schmiegel W: Mesalazine causes a mitotic arrest and induces caspase-dependent apoptosis in colon carcinoma cells. Carcinogenesis 2003;24:443–451.
  43. Bantel H, Berg C, Vieth M, Stolte M, Kruis W, Schultze-Osthoff K: Mesalazine inhibits activation of transcription factor NF-kappaB in inflamed mucosa of patients with ulcerative colitis. Am J Gastroenterol 2000;95:3452–3457.
  44. Matula S, Croog V, Itzkowitz S, Harpaz N, Bodian C, Hossain S, Ullman T: Chemoprevention of colorectal neoplasia in ulcerative colitis: the effect of 6-mercaptopurine. Clin Gastroenterol Hepatol 2005;3:1015–1021.
  45. Schmiegel W, Pox CP, Reiser M; German 5-ASA Polyp Prevention Study Group (GAPPS): Effect of 5-aminosalicylate (5-ASA) on the recurrence rate of sporadic colorectal adenomas. Gastroenterology 2004;126(suppl 2):A452.
  46. Terdiman JP, Gumm J, Kim YS, Sleisenger MH, Weinberg V, Colson S, Verghese V, Hayes A, Johnson LK: Chemoprevention of colonic polyps by balsalazide: an exploratory double blind placebo controlled study. Gastroenterology 2004 126(suppl 2):A388.
  47. Giovannucci E, Stampfer MJ, Colditz GA, Hunter DJ, Fuchs C, Rosner BA, Speizer FE, Willett WC: Multivitamin use, folate, and colon cancer in women in the Nurses’ Health Study. Ann Intern Med 1998;129:517–524.
  48. Terry P, Jain M, Miller AB, Howe GR, Rohan TE: Dietary intake of folic acid and colorectal cancer risk in a cohort of women. Int J Cancer 2002;97:864–867.
  49. La Vecchia C, Negri E, Pelucchi C, Franceschi S: Dietary folate and colorectal cancer. Int J Cancer 2002;102:545–547.
  50. Hayashi I, Sohn KJ, Stempak JM, Croxford R, Kim YI: Folate deficiency induces cell-specific changes in the steady-state transcript levels of genes involved in folate metabolism and 1-carbon transfer reactions in human colonic epithelial cells. J Nutr 2007;137:607–613.
  51. Kim YI: Folate and colorectal cancer: an evidence-based critical review. Mol Nutr Food Res 2007;51:267–292.
  52. Novakovic P, Stempak JM, Sohn KJ, Kim YI: Effects of folate deficiency on gene expression in the apoptosis and cancer pathways in colon cancer cells. Carcinogenesis 2006;27:916–924.
  53. De Vogel S, van Engeland M, Lüchtenborg M, de Bruïne AP, Roemen GM, Lentjes MH, Goldbohm RA, van den Brandt PA, de Goeij AF, Weijenberg MP: Dietary folate and APC mutations in sporadic colorectal cancer. J Nutr 2006;136:3015–3021.
  54. Kune G, Watson L: Colorectal cancer protective effects and the dietary micronutrients folate, methionine, vitamins B6, B12, C, E, selenium, and lycopene. Nutr Cancer 2006;56:11–21.
  55. Bostick RM, Potter JD, McKenzie DR, Sellers TA, Kushi LH, Steinmetz KA, Folsom AR: Reduced risk of colon cancer with high intake of vitamin E: the Iowa Women’s Health Study. Cancer Res 1993;53:4230–4237.
  56. Bjelakovic G, Nikolova D, Simonetti RG, Gluud C: Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. Lancet 2004;364:1219–1228.
  57. Gorham ED, Garland CF, Garland FC, Grant WB, Mohr SB, Lipkin M, Newmark HL, Giovannucci E, Wei M, Holick MF: Vitamin D and prevention of colorectal cancer. J Steroid Biochem Mol Biol 2005;97:179–194.
  58. Willett WC, Stampfer MJ, Colditz GA, Rosner BA, Speizer FE: Relation of meat, fat, and fiber intake to the risk of colon cancer in a prospective study among women. N Engl J Med 1990;323:1664–1672.
  59. Nagengast FM, Grubben MJ, van Munster IP: Role of bile acids in colorectal carcinogenesis. Eur J Cancer 1995;31A:1067–1070.
  60. Baron JA, Beach M, Mandel JS, van Stolk RU, Haile RW, Sandler RS, Rothstein R, Summers RW, Snover DC, Beck GJ, Bond JH, Greenberg ER; Calcium Polyp Prevention Study Group: Calcium supplements for the prevention of colorectal adenomas. N Engl J Med 1999;340:101–107.
  61. Bonithon-Kopp C, Kronborg O, Giacosa A, Rath U, Faivre J; European Cancer Prevention Organisation Study Group: Calcium and fibre supplementation in prevention of colorectal adenoma recurrence: a randomised intervention trial. Lancet 2000;356:1300–1306.
  62. Wu K, Willett WC, Fuchs CS, Colditz GA, Giovannucci EL: Calcium intake and risk of colon cancer in women and men. J Natl Cancer Inst 2002;94:437–446.
  63. Wactawski-Wende J, Kotchen JM, Anderson GL, Assaf AR, Brunner RL, O’Sullivan MJ, Margolis KL, Ockene JK, Phillips L, Pottern L, Prentice RL, Robbins J, Rohan TE, Sarto GE, Sharma S, Stefanick ML, Van Horn L, Wallace RB, Whitlock E, Bassford T, Beresford SA, Black HR, Bonds DE, Brzyski RG, Caan B, Chlebowski RT, Cochrane B, Garland C, Gass M, Hays J, Heiss G, Hendrix SL, Howard BV, Hsia J, Hubbell FA, Jackson RD, Johnson KC, Judd H, Kooperberg CL, Kuller LH, LaCroix AZ, Lane DS, Langer RD, Lasser NL, Lewis CE, Limacher MC, Manson JE; Women’s Health Initiative Investigators: Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med 2006;354:684–696.
  64. Forman MR, Levin B: Calcium plus vitamin D3 supplementation and colorectal cancer in women. N Engl J Med 2006;354:752–754.
  65. Kim YI: AGA technical review: impact of dietary fibre on colon cancer occurrence. Gastroenterology 2000;118:1235–1257.
  66. Michels KB, Giovannucci E, Joshipura KJ, Rosner BA, Stampfer MJ, Fuchs CS, Colditz GA, Speizer FE, Willett WC: Prospective study of fruit and vegetable consumption and incidence of colon and rectal cancers. J Natl Cancer Inst 2000;92:1740–1752.
  67. Howe GR, Benito E, Castelleto R, Cornée J, Estève J, Gallagher RP, Iscovich JM, Deng-ao J, Kaaks R, Kune GA, Kune S, L’Abbé KA, Lee HP, Lee M, Millar AB, Peters RK, Potter JD, Riboli E, Slattery M, Trichopoulos D, Tuyns A, Tzonou A, Whittemore AS, Wu-Williams AH, Shu Z: Dietary intake of fiber and decreased risk of cancers of the colon and rectum: evidence from the combined analysis of 13 case-control studies. J Natl Cancer Inst 1992;84:1887–1896.
  68. Fuchs CS, Giovannucci EL, Colditz GA, Hunter DJ, Stampfer MJ, Rosner B, Speizer FE, Willett WC: Dietary fiber and the risk of colorectal cancer and adenoma in women. N Engl J Med 1999;340:169–176.
  69. Giovannucci E, Rimm EB, Stampfer MJ, Colditz GA, Ascherio A, Willett WC: Intake of fat, meat, and fibre in relation to risk of colon cancer in men. Cancer Res 1994;54:2390–2397.
  70. Steinmetz KA, Kushi LH, Bostick RM, Folsom AR, Potter JD: Vegetables, fruit, and colon cancer in the Iowa Women’s Health Study. Am J Epidemiol 1994;139:1–15.
  71. Beresford SA, Johnson KC, Ritenbaugh C, Lasser NL, Snetselaar LG, Black HR, Anderson GL, Assaf AR, Bassford T, Bowen D, Brunner RL, Brzyski RG, Caan B, Chlebowski RT, Gass M, Harrigan RC, Hays J, Heber D, Heiss G, Hendrix SL, Howard BV, Hsia J, Hubbell FA, Jackson RD, Kotchen JM, Kuller LH, LaCroix AZ, Lane DS, Langer RD, Lewis CE, Manson JE, Margolis KL, Mossavar-Rahmani Y, Ockene JK, Parker LM, Perri MG, Phillips L, Prentice RL, Robbins J, Rossouw JE, Sarto GE, Stefanick ML, Van Horn L, Vitolins MZ, Wactawski-Wende J, Wallace RB, Whitlock E: Low-fat dietary pattern and risk of colorectal cancer: the Women’s Health Initiative Randomized Controlled Dietary Modification Trial. JAMA 2006;295:643–654.
  72. Bingham SA, Day NE, Luben R, Ferrari P, Slimani N, Norat T, Clavel-Chapelon F, Kesse E, Nieters A, Boeing H, Tjonneland A, Overvad K, Martinez C, Dorronsoro M, Gonzalez CA, Key TJ, Trichopoulou A, Naska A, Vineis P, Tumino R, Krogh V, Bueno-de-Mesquita HB, Peeters PH, Berglund G, Hallmans G, Lund E, Skeie G, Kaaks R, Riboli E; European Prospective Investigation into Cancer and Nutrition: Dietary fibre in food and protection against colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC): an observational study. Lancet 2003;361:1496–1501.
  73. Peters U, Sinha R, Chatterjee N, Subar AF, Ziegler RG, Kulldorff M, Bresalier R, Weissfeld JL, Flood A, Schatzkin A, Hayes RB; Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Project Team: Dietary fibre and colorectal adenoma in a colorectal cancer early detection programme. Lancet 2003;361:1491–1495.
  74. Singh PN, Fraser GE: Dietary risk factors for colon cancer in a low-risk population. Am J Epidemiol 1998;148:761–774.
  75. Jacobs ET, Giuliano AR, Roe DJ, Guillen-Rodriguez JM, Hess LM, Alberts DS, Martinez ME: Intake of supplemental and total fiber and risk of colorectal adenoma recurrence in the wheat bran fiber trial. Cancer Epidemiol Biomark Prev 2002;11:906–914.
  76. Goldbohm RA, van den Brandt PA, van’t Veer P, Brants HA, Dorant E, Sturmans F, Hermus RJ: A prospective cohort study on the relation between meat consumption and the risk of colon cancer. Cancer Res 1994;54:718–723.
  77. Sugimura T: Carcinogenicity of mutagenic heterocyclic amines formed during the cooking process. Mutat Res 1985;150:33–41.
  78. Reddy BS, Hedges AR, Laakso K, et al: Metabolic epidemiology of large bowel cancer: fecal bulk and constituents of high-risk North American and low-risk Finnish population. Cancer 1978;42:2832–2838.
  79. Neugut AI, Garbowski GC, Lee WC, Murray T, Nieves JW, Forde KA, Treat MR, Waye JD, Fenoglio-Preiser C: Dietary risk factors for the incidence and recurrence of colorectal adenomatous polyps: a case-control study. Ann Intern Med 1993;118:91–95.
  80. Shepherd J, Blauw GJ, Murphy MB, Bollen EL, Buckley BM, Cobbe SM, Ford I, Gaw A, Hyland M, Jukema JW, Kamper AM, Macfarlane PW, Meinders AE, Norrie J, Packard CJ, Perry IJ, Stott DJ, Sweeney BJ, Twomey C, Westendorp RG; PROSPER study group: PROspective Study of Pravastatin in the Elderly at Risk: Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002;360:1623–1630.
  81. Swamy MV, Cooma I, Reddy BS, Rao CV: Lamin B, caspase-3 activity, and apoptosis induction by a combination of HMG-CoA reductase inhibitor and COX-2 inhibitors: a novel approach in developing effective chemopreventive regimens. Int J Oncol 2002;20:753–759.
  82. Agarwal B, Rao CV, Bhendwal S, Ramey WR, Shirin H, Reddy BS, Holt PR: Lovastatin augments sulindac-induced apoptosis in colon cancer cells and potentiates chemopreventive effects of sulindac. Gastroenterology 1999;117:838–847.
  83. Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, Brown L, Warnica JW, Arnold JMO, Wun C, Davis BR, Braunwald E: The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 1996;335:1001–1009.
  84. Pedersen TR, Berg K, Cook TJ, Faergeman O, Haghfelt T, Kjekshus J, Miettinen T, Musliner TA, Olsson AG, Pyorala K, Thorgeirsson G, Tobert JA, Wedel H, Wilhelmsen L: Safety and tolerability of cholesterol lowering agents with simvastatin during 5 years in the Scandinavian Simvastatin Survival Study. Arch Intern Med 1996;156:2085–2092.
  85. Poynter JN, Gruber SB, Higgins PDR, 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.
  86. Jacobs EJ, Rodriguez C, Brady KA, Connell CJ, Thun MJ, Calle EE: Cholesterol-lowering drugs and colorectal cancer incidence in a large United States cohort. J Natl Cancer Inst 2006;98:69–72.
  87. Dale KM, Coleman CI: Henyan NN, Kluger J, White CM: Statins and cancer risk: a meta-analysis. JAMA 2006;295:74–80.
  88. 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.
  89. Jacobs ET, Jiang R, Alberts DS, Greenberg ER, Gunter EW, Karagas MR, Lanza E, Ratnasinghe L, Reid ME, Schatzkin A, Smith-Warner SA, Wallace K, Martinez ME: Selenium and colorectal adenoma: results of a pooled analysis. J Natl Cancer Inst 2004;96:1669–1675.
  90. Clark LC, Combs GF Jr, Turnbull BW, Slate EH, Chalker DK, Chow J, Davis LS, Glover RA, Graham GF, Gross EG, Krongrad A, Lesher JL Jr, Park HK, Sanders BB Jr, Smith CL, Taylor JR; Nutritional Prevention of Cancer Study Group: Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin: a randomized controlled trial. J Am Med Assoc 1996;276:1957–1963.
  91. Rayman MP: The importance of selenium to human health. Lancet 2000;356:233–241.
  92. Pardi DS, Loftus EV Jr, Kremers WK, Keach J, Lindor KD: Ursodeoxycholic acid as a chemopreventive agent in patients with ulcerative colitis and primary sclerosing cholangitis. Gastroenterology 2003;124:889–893.
  93. Serfaty L, De Leusse A, Rosmorduc O, Desaint B, Flejou JF, Chazouilleres O, Poupon RE, Poupon R: Ursodeoxycholic acid therapy and the risk of colorectal adenoma in patients with primary biliary cirrhosis: an observational study. Hepatology 2003;38:203–209.
  94. Alberts DS, Martínez ME, Hess LM, Einspahr JG, Green SB, Bhattacharyya AK, Guillen J, Krutzsch M, Batta AK, Salen G, Fales L, Koonce K, Parish D, Clouser M, Roe D, Lance P; Phoenix and Tucson Gastroenterologist Networks: Phase III trial of ursodeoxycholic acid to prevent colorectal adenoma recurrence. J Natl Cancer Inst 2005; 97:846–853.
  95. Chlebowski RT, Wactawski-Wende J, Ritenbaugh C, Hubbell FA, Ascensao J, Rodabough RJ, Rosenberg CA, Taylor VM, Harris R, Chen C, Adams-Campbell LL, White E; Women’s Health Initiative Investigators: Estrogen plus progestin and colorectal cancer in postmenopausal women. N Engl J Med 2004;350:991–1004.
  96. O’dwyer PJ, Benson AB III: Epidermal growth factor receptor-targeted therapy in colorectal cancer. Semin Oncol 2002;29 (suppl 14):10–17.
  97. Sirotnak FM: Studies with ZD1839 in preclinical models. Semin Oncol 2003;30 (suppl 1):12–20.

    External Resources

  98. Torrance CJ, Jackson PE, Montgomery E, Kinzler KW, Vogelstein B, Wissner A, Nunes M, Frost P, Discafani CM: Combinatorial chemoprevention of intestinal neoplasia. Nat Med 2000;6:1024–1028.
  99. Meyskens FL Jr, Gerner EW, Emerson S, Pelot D, Durbin T, Doyle K, Lagerberg W: Effect of alpha-difluoromethylornithine on rectal mucosal levels of polyamines in a randomized, double-blinded trial for colon cancer prevention. J Natl Cancer Inst 1998;90:1212–1218.
  100. Jacoby RF, Cole CE, Tutsch K, Newton MA, Kelloff G, Hawk ET, Lubet RA: Chemopreventive efficacy of combined piroxicam and difluoromethylornithine treatment of Apc mutant Min mouse adenomas, and selective toxicity against Apc mutant embryos. Cancer Res 2000;60:1864–1870.
  101. www.fda.gov/ohrms/dockets/ac/05/slides/2005–4191S1_09_Pfizer.ppt