Prevention and Early Detection of Colorectal Cancer — New Horizons

  • Gad Rennert
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 174)

Abstract

Colorectal cancer is potentially one of the most preventable malignancies. Nutritional awareness (low fat, low red meat, high fruits and vegetables) and regular physical activity have major potential for primary prevention of this malignancy, while early detection technologies have the potential of both influencing mortality from colorectal cancer as well as enhancing primary prevention through detection and removal of lesions that could potentially develop into cancer. While the potential for prevention is large, its materialization is far from being optimal. The large-scale lifestyle changes in the population necessary to reduce colorectal cancer rates are hard to achieve, and most of the early detection technologies are either invasive or otherwise nonappealing to the population. Thus, without abandoning the proven prevention methods, new avenues need to be investigated to deal with this malignancy, which carries both high morbidity and high mortality. Such new avenues can now be followed, both in prevention and detection. Chemoprevention, or the use of medications to prevent disease, has now been extensively explored in colorectal cancer. Some of these interventions, such as supplemental fibers, have failed to demonstrate the anticipated effect, while others such as calcium supplementation have been shown to reduce formation of premalignant lesions, polyps, or adenomas. Data accumulating in recent years have suggested that aspirin, nonsteroidal anti-inflammatory drugs, and selective COX-II inhibitors all have a potential to reduce both colorectal cancer and colorectal adenomas. Issues of safety and therapeutic indexes have recently come up as barriers to the use of COX-II inhibitors, and have again drawn attention to aspirin as a potential drug of choice. Association studies have also shown a major potential role for statins in colorectal cancer prevention. New methodologies in cancer detection involve the introduction of colonography or virtual colonoscopy, and the development of methods of detection of genetic somatic mutations in feces or peripheral blood. While radiological techniques currently avoid the need for premedication and are less invasive, they currently still require similar gut cleansing to colonoscopy, can also lead to perforation, are costly, and carry a non-negligible exposure to radiation. Genetic analysis of the stool for mutations in tumor cells is evolving as a promising technique, struggling to achieve both high sensitivity and high specificity with the right combination of mutations sought. With all of these developments taking place, the near future will undoubtedly bring about the expected reduction in colorectal cancer mortality.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ahlquist DA, Skoletsky JE, Boynton KA, Harrington JJ, Mahoney DW, Pierceall WE, Thibodeau SN, Shuber AP (2000) Colorectal cancer screening by detection of altered human DNA in stool: feasibility of a multitarget assay panel. Gastroenterology 119:1219–1227PubMedCrossRefGoogle Scholar
  2. Ajani UA, Ford ES, Greenland KJ, Giles WH, Mokdad AH (2006) Aspirin use among U.S. Adults behavioral risk factor surveillance system. Am J Prev Med 30:74–77PubMedCrossRefGoogle Scholar
  3. 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 (1999) Calcium supplements for the prevention of colorectal adenomas. Calcium Polyp Prevention Study Group. N Engl J Med 340:101–107PubMedCrossRefGoogle Scholar
  4. 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 (2003) A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med 348:891–899PubMedCrossRefGoogle Scholar
  5. Benamouzig R, Deyra J, Martin A, Girard B, Jullian E, Piednoir B, Couturier D, Coste T, Little J, Chaussade S (2003) Daily soluble aspirin and prevention of colorectal adenoma recurrence: one-year results of the APACC trial. Gastroenterology 125:328–336PubMedCrossRefGoogle Scholar
  6. Beresford SAA, Johnson KC, Ritenbaugh C et al. (2006) Low-fat dietary pattern and risk of colorectal cancer. JAMA 295:643–654PubMedCrossRefGoogle Scholar
  7. Bingham S (2006) The fibre-folate debate in colo-rectal cancer. Proc Nutr Soc 65:19–23PubMedCrossRefGoogle Scholar
  8. Bodmer WF (2006) Cancer genetics: colorectal cancer as a model. J Hum Genet 51:391–396PubMedCrossRefGoogle Scholar
  9. Boon EM, Keller JJ, Wormhoudt TA, Giardiello FM, Offerhaus GJ, van der Neut R, Pals ST (2004) Sulindac targets nuclear beta-catenin accumulation and Wnt signalling in adenomas of patients with familial adenomatous polyposis and in human colorectal cancer cell lines. Br J Cancer 90:224–229PubMedCrossRefGoogle Scholar
  10. Brenner DE, Rennert G (2005) Fecal DNA biomarkers for the detection of colorectal neoplasia: Attractive, but is it feasible? J Natl Cancer Inst 97:1107–1109PubMedCrossRefGoogle Scholar
  11. Bresalier RS, Sandler RS, Quan H, Bolognese JA, Oxenius B, Horgan K, Lines C, Riddell R, Morton D, Lanas A, Konstam MA, Baron JA; Adenomatous Polyp Prevention on Vioxx (APPROVe) Trial Investigators (2005) Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med 352:1092–1102PubMedCrossRefGoogle Scholar
  12. Canadian Task Force on Preventive Health Care (2001) Colorectal cancer screening. Recommendation statement from the Canadian Task Force on Preventive Health Care. CMAJ 165:206–208Google Scholar
  13. Chan AT, Giovannucci EL, Meyerhardt JA, Schernhammer ES, Curhan GC, Fuchs CS (2005) Long-term use of aspirin and nonsteroidal anti-inflammatory drugs and risk of colorectal cancer. JAMA 294:914–923PubMedCrossRefGoogle Scholar
  14. Chao A, Thun MJ, Connell CJ, McCullough ML, Jacobs EJ, Flanders WD, Rodriguez C, Sinha R, Calle EE (2005) Meat consumption and risk of colorectal cancer. JAMA 293:172–182PubMedCrossRefGoogle Scholar
  15. Charames GS, Bapat B (2006) Cyclooxygenase-2 knockdown by RNA interference in colon cancer. Int J Oncol 28:543–549PubMedGoogle Scholar
  16. Cook NR, Lee IM, Gaziano JM, Gordon D, Ridker PM, Manson JE, Hennekens CH, Buring JE (2005) Low-dose aspirin in the primary prevention of cancer: the Women’s Health Study: a randomized controlled trial. JAMA 294:47–55PubMedCrossRefGoogle Scholar
  17. Dale KM, Coleman CI, Henyan NN, Kluger J, White CM (2006) Statins and cancer risk: a meta-analysis. JAMA 295:74–80PubMedCrossRefGoogle Scholar
  18. Davies RJ, Miller R, Coleman N (2005) Colorectal cancer screening: prospects for molecular stool analysis. Nat Rev Cancer 5:199–209PubMedCrossRefGoogle Scholar
  19. Din FV, Dunlop MG, Stark LA (2004) Evidence for colorectal cancer cell specificity of aspirin effects on NF kappa B signalling and apoptosis. Br J Cancer 91:381–388PubMedGoogle Scholar
  20. Dong SM, Traverso G, Johnson C, Geng L, Favis R, Boynton K, Hibi K, Goodman SN, D’Allessio M, Paty P, Hamilton SR, Sidransky D, Barany F, Levin B, Shuber A, Kinzler KW, Vogelstein B, Jen J (2001) Detecting colorectal cancer in stool with the use of multiple genetic targets. J Natl Cancer Inst 93:858–865PubMedCrossRefGoogle Scholar
  21. Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61:759–767PubMedCrossRefGoogle Scholar
  22. Frezza EE, Wachtel MS, Chiriva-Internati M (2006) Influence of obesity on the risk of developing colon cancer. Gut 55:285–291PubMedCrossRefGoogle Scholar
  23. Gann PH, Manson JE, Glynn RJ, Buring JE, Hennekens CH (1993) Low-dose aspirin and incidence of colorectal tumors in a randomized trial. J Natl Cancer Inst 85:1220–1224PubMedCrossRefGoogle Scholar
  24. Grau MV, Baron JA, Barry EL, Sandler RS, Haile RW, Mandel JS, Cole BF (2005) Interaction of calcium supplementation and nonsteroidal anti-inflammatory drugs and the risk of colorectal adenomas. Cancer Epidemiol Biomarkers Prev 14:2353–2358PubMedCrossRefGoogle Scholar
  25. Hull MA (2005) Cyclooxygenase-2: how good is it as a target for cancer chemoprevention? Eur J Cancer 41:1854–1863PubMedCrossRefGoogle Scholar
  26. Imperiale TF, Ransohoff DF, Itzkowitz SH, Turnbull BA, Ross ME (2004) Fecal DNA versus fecal occult blood for colorectal cancer screening in an averagerisk population. N Engl J Med 351:2704–2714PubMedCrossRefGoogle Scholar
  27. Jacobs EJ, Rodriguez C, Brady KA, Connell CJ, Thun MJ, Calle EE (2006) Cholesterol-lowering drugs and colorectal cancer incidence in a large United States cohort. J Natl Cancer Inst 98:69–72PubMedCrossRefGoogle Scholar
  28. Koshiji M, Yonekura Y, Saito T, Yoshioka K (2002) Microsatellite analysis of fecal DNA for coilorectal cancer detection. J Surg Oncol 80:34–40PubMedCrossRefGoogle Scholar
  29. Larsson SC, Giovannucci E, Wolk A (2005) A prospective study of dietary folate intake and risk of colorectal cancer: modification by caffeine intake and cigarette smoking. Cancer Epidemiol Biomarkers Prev 14:740–743PubMedCrossRefGoogle Scholar
  30. Larsson SC, Rafter J, Holmberg L, Bergkvist L, Wolk A (2005) Red meat consumption and risk of cancers of the proximal colon, distal colon and rectum: the Swedish Mammography Cohort. Int J Cancer 113:829–834PubMedCrossRefGoogle Scholar
  31. Lev Z, Kislitsin D, Rennert G, Lerner A (2000) Utilization of K-ras Mutations Identified in Stool DNA for the Early Detection of Colorectal Cancer. J Cell Biochem 34[Suppl]:35–39CrossRefGoogle Scholar
  32. Mulhall BP, Veerappan GR, Jackson JL (2005) Metaanalysis: computed tomographic colonography. Ann Intern Med 142:635–650PubMedGoogle Scholar
  33. Park Y, Hunter DJ, Spiegelman D, Bergkvist L, Berrino F, van den Brandt PA, Buring JE, Colditz GA, Freudenheim JL, Fuchs CS, Giovannucci E, Goldbohm RA, Graham S, Harnack L, Hartman AM, Jacobs DR Jr, Kato I, Krogh V, Leitzmann MF, McCullough ML, Miller AB, Pietinen P, Rohan TE, Schatzkin A, Willett WC, Wolk A, Zeleniuch-Jacquotte A, Zhang SM, Smith-Warner SA (2005) Dietary fiber intake and risk of colorectal cancer: a pooled analysis of prospective cohort studies. JAMA 294:2849–2857PubMedCrossRefGoogle Scholar
  34. Phillips RK, Wallace MH, Lynch PM, Hawk E, Gordon GB, Saunders BP, Wakabayashi N, Shen Y, Zimmerman S, Godio L, Rodrigues-Bigas M, Su LK, Sherman J, Kelloff G, Levin B, Steinbach G; FAP Study Group (2002) A randomised, double blind, placebo controlled study of celecoxib, a selective cyclooxygenase 2 inhibitor, on duodenal polyposis in familial adenomatous polyposis. Gut 50:857–860PubMedCrossRefGoogle Scholar
  35. Pickhardt PJ, Choi JR, Hwang I, Butler JA, Puckett ML, Hildebrandt HA, Wong RK, Nugent PA, Mysliwiec PA, Schindler WR (2003) Computed tomographic virtual colonoscopy to screen for colorectal neoplasia in asymptomatic adults. N Engl J Med 349:2191–2200PubMedCrossRefGoogle Scholar
  36. Potter JD, Hunter D (2002) Colorectal cancer. In: Adami HO, Hunter D, Trichopoulos D (eds) Textbook of cancer epidemiology. Oxford University Press, Oxford, pp 188–211Google Scholar
  37. Poynter JN, Gruber SB, Higgins PDR, Almog R, Bonner JD, Rennert HS, Low M, Greenson JK, Rennert G (2005) Statins and the Risk of Colorectal Cancer. N Engl J Med 352:2184–2192PubMedCrossRefGoogle Scholar
  38. Rapp K, Schroeder J, Klenk J, Stoehr S, Ulmer H, Concin H, Diem G, Oberaigner W, Weiland SK (2005) Obesity and incidence of cancer: a large cohort study of over 145,000 adults in Austria. Br J Cancer 93:1062–1067PubMedCrossRefGoogle Scholar
  39. Reddy BS, Patlolla JM, Simi B, Wang SH, Rao CV (2005) Prevention of colon cancer by low doses of celecoxib, a cyclooxygenase inhibitor, administered in diet rich in omega-3 polyunsaturated fatty acids. Cancer Res 65:8022–8027PubMedCrossRefGoogle Scholar
  40. Rengucci C, Maiolo P, Saragoni L, Zoli W, Amadori D, Calistri D (2001) Multiple detection of genetic alterations in tumors and stool. Clin Cancer Res 7:590–593PubMedGoogle Scholar
  41. Rennert G (2002) Dietary intervention studies and cancer prevention. Eur J Cancer Prev 11:419–425PubMedCrossRefGoogle Scholar
  42. Rennert G (2006) Are we taking the right approach in planning chemoprevention studies? Nat Clin Pract Oncol 3:464–465PubMedCrossRefGoogle Scholar
  43. Rennert G, Brenner D, Rennert HS, Lev Z (2006) K-ras in stool from test cards improves the positive predictive value of FOBT. Cancer Epidemiol Biomarkers Prev (submitted)Google Scholar
  44. Sandler RS, Halabi S, Baron JA, Budinger S, Paskett E, Keresztes R, Petrelli N, Pipas JM, Karp DD, Loprinzi CL, Steinbach G, Schilsky R (2003) A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. N Engl J Med 348:883–90PubMedCrossRefGoogle Scholar
  45. Sansbury LB, Millikan RC, Schroeder JC, Moorman PG, North KE, Sandler RS (2005) Use of nonsteroidal antiinflammatory drugs and risk of colon cancer in a population-based, case-control study of African Americans and Whites. Am J Epidemiol 162:548–558PubMedCrossRefGoogle Scholar
  46. Slattery ML, Neuhausen SL, Hoffman M, Caan B, Curtin K, Ma KN, Samowitz W (2004a) Dietary calcium, vitamin D, VDR genotypes and colorectal cancer. Int J Cancer 111:750–756PubMedCrossRefGoogle Scholar
  47. Slattery ML, Samowitz W, Hoffman M, Ma KN, Levin TR, Neuhausen S (2004b) Aspirin, NSAIDs, and colorectal cancer: possible involvement in an insulin-related pathway. Cancer Epidemiol Biomarkers Prev 13:538–545PubMedGoogle Scholar
  48. 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 (2005) Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med 352:1071–1080PubMedCrossRefGoogle Scholar
  49. Tagore KS Lawson MJ, Yucaitis JA, Gage R, Orr T, Shuber AP, Ross ME (2003) Sensitivity and specificity of a stool DNA multitarget assay panel for the detection of advanced colorectal neoplasia. Clin Colorectal Cancer 3:47–53PubMedCrossRefGoogle Scholar
  50. Teeling M, Bennett K, Feely J (2005) The influence of guidelines on the use of statins: analysis of prescribing trends 1998–2002. Br J Clin Pharmacol 59:227–232PubMedCrossRefGoogle Scholar
  51. Thun MJ, Henley SJ, Patrono C (2002) Nonsteroidal anti-inflammatory drugs as anticancer agents: mechanistic, pharmacologic, and clinical issues. J Natl Cancer Inst 94:252–266PubMedGoogle Scholar
  52. Wald NJ, Law MR (2003) A strategy to reduce cardiovascular disease by more than 80%. BMJ 326:1419PubMedCrossRefGoogle Scholar
  53. Wallace K, Baron JA, Karagas MR, Cole BF, Byers T, Beach MA, Pearson LH, Burke CA, Silverman WB, Sandler RS (2005) The association of physical activity and body mass index with the risk of large bowel polyps. Cancer Epidemiol Biomarkers Prev 14:2082–2086PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2007

Authors and Affiliations

  • Gad Rennert
    • 1
  1. 1.CHS National Cancer Control CenterCarmel Medical CenterHaifaIsrael

Personalised recommendations