Current Colorectal Cancer Reports

, Volume 8, Issue 1, pp 51–56

Prevention of Colorectal Cancer by Aspirin and/or Calcium: Efficacy, Mechanisms, and Cost Effectiveness

  • Barbara C. Pence
  • Eric J. Belasco
  • Conrad P. Lyford
Molecular Epidemiology (MJ Wargovich, Section Editor)
  • 109 Downloads

Abstract

Chemoprevention of colorectal cancer (CRC) by aspirin use or calcium supplementation has been studied for almost two decades. Recently, the use of aspirin has been reported to be efficacious for the chemoprevention of CRC at the lowest dose ever, one that corresponds to that recommended for the primary prevention of cardiovascular disease. There is also new evidence that aspirin at higher doses may be helpful in controlling familial adenomatous polyposis (FAP). Several cost effectiveness studies have emerged to demonstrate that use of aspirin in combination with colonoscopy is cost-effective compared with colonoscopy alone in prevention of CRC. Likewise, calcium supplementation in a chemoprevention strategy also has been shown to be cost-effective when used alone or in combination with colonoscopy in CRC prevention, compared to natural history. The chemopreventive mechanisms of these agents continue to be studied, and prominent molecular targets for aspirin are cyclooxygenase (COX)-2, and perhaps COX-1, as well as the calcium-sensing receptor (CaSR) as the likely target for calcium supplementation. The evidence is compelling for the widespread use of these non-prescription agents, either alone or in combination, for either primary prevention of CRC in the general population, or as part of a colonoscopy surveillance program in high-risk populations with a prior adenoma.

Keywords

Colorectal cancer Chemoprevention Colonoscopy Aspirin Calcium Cost-effectiveness Markov simulation COX-2 Calcium-sensing receptor 

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1. •
    Pence BC, Buddingh F. Inhibition of dietary fat-promoted colon carcinogenesis in rats by supplemental calcium or vitamin D3. Carcinogenesis. 1988;9:1887–90. This is the first article reporting that dietary calcium can prevent colon cancer in a preclinical study.CrossRefGoogle Scholar
  2. 2.
    Carroll C, Cooper K, Papioannou D, et al. Supplemental calcium in the chemoprevention of colorectal cancer: a systematic review and meta-analysis. Clin Ther. 2010;32:789–803.PubMedCrossRefGoogle Scholar
  3. 3. ••
    Baron JA, Cole BF, Sandler RS, et al. A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med. 2003;348:891–9. This randomized controlled trial showed that aspirin (81 mg/day) had a moderate chemopreventive effect on adenomas in the colon.PubMedCrossRefGoogle Scholar
  4. 4.
    Dube C, Rostom A, Lewin G, et al. The use of aspirin for primary prevention of colorectal cancer: a systematic review prepared for the U.S. Preventive Services Task Force. Ann Intern Med. 2007;146:365–75.PubMedGoogle Scholar
  5. 5. ••
    Rothwell PM, Wilson M, Elwin C-E, et al. Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomized trials. Lancet. 2010;376:1741–50. Aspirin taken for 5 years or longer at a dose of 75 mg/day reduced long-term incidence and mortality for CRC.PubMedCrossRefGoogle Scholar
  6. 6.
    Benamouzig R, Uzzan B, Deyra J, et al. Prevention by aspirin of colorectal adenoma recurrence: some advances and latest results of the APACC Trial. Curr Colorectal Cancer Rep. 2011;7:33–41.CrossRefGoogle Scholar
  7. 7. •
    Burn J, Bishop DT, Chapman RD, et al. A randomized placebo-controlled prevention trial of aspirin and/or resistant starch in young people with familial adenomatous polyposis. Cancer Prev Res. 2011;4:655–65. This is the first repot of aspirin effectiveness in the clinical management of FAP patients.CrossRefGoogle Scholar
  8. 8.
    Chan AT. Aspirin and familial adenomatous polyposis: coming full circle. Cancer Prev Res. 2011;4:623–7.CrossRefGoogle Scholar
  9. 9. •
    Din FVN, Theodoratou E, Farrington SM, et al. Effect of aspirin and NSAIDS on risk and survival from colorectal cancer. Gut. 2010;59:1670–9. This is the first study to demonstrate a protective effect against CRC of 75 mg aspirin/day, after only 5 years’ use, in the general population.PubMedCrossRefGoogle Scholar
  10. 10.
    Baron JA, Beach M, Mandel JS, et al. Calcium supplements for the prevention of colorectal adenomas. N Engl J Med. 1999;340:101–7.PubMedCrossRefGoogle Scholar
  11. 11.
    Wactawski-Wende J, Kotchen JM, Anderson GL, et al. Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med. 2006;354:684–96.PubMedCrossRefGoogle Scholar
  12. 12. •
    Grau MV, Baron JA, Barry EL, et al. Interaction of calcium supplementation and nonsteroidal anti-inflammatory drugs and the risk of colorectal adenomas. Cancer Epidemiol Biomarkers Prev. 2005;14:2353–8. This article showed a synergistic interaction between aspirin and calcium chemoprevention in two polyp prevention trials.PubMedCrossRefGoogle Scholar
  13. 13.
    Dupont AW, Arguedas MR, Wilcox CM. Aspirin chemoprevention in patients with increased risk for colorectal cancer: a cost-effectiveness analysis. Aliment Pharmacol Ther. 2007;26:431–41.PubMedCrossRefGoogle Scholar
  14. 14. ••
    Hassan C, Rex DK, Cooper GS, et al. Primary prevention of colorectal cancer with low-dose aspirin in combination with endoscopy: a cost-effectiveness analysis. Gut. 2011; doi:10.1136/gutjnl-2011-300206. This article concluded that the economic savings in CRC care compensated for the additional cost of low-dose aspirin and aspirin-related complications.
  15. 15. ••
    Squires H, Tappenden P, Cooper K, et al. Cost-effectiveness of aspirin, celecoxib, and calcium chemoprevention for colorectal cancer. Clin Ther. 2011;33:1289–305. This article is a cost-effectiveness analysis which indicates that calcium chemoprevention has a higher probability than aspirin for providing value for money within the general population, and that celecoxib is not considered to be cost-effective.PubMedCrossRefGoogle Scholar
  16. 16.
    Shaukat A, Parekc M, Lipscomb J, et al. Can calcium chemoprevention of adenoma recurrence substitute or serve as an adjunct for colonoscopic surveillance? Int J Technol Assess Health Care. 2009;25:222–31.PubMedCrossRefGoogle Scholar
  17. 17.
    Kraus S, Arber N. Cyclooxygenase-2 expression and recurrence of colorectal adenomas: effect of aspirin chemoprevention. Curr Colorectal Cancer Rep. 2011;7:5–7.CrossRefGoogle Scholar
  18. 18.
    Chan AT, Ogino S, Fuchs CS. Aspirin and the risk of colorectal cancer in relation to the expression of COX-2. N Eng J Med. 2007;356:2131–42.CrossRefGoogle Scholar
  19. 19.
    Ahearn TU, McCollough ML, Flanders WD, et al. A randomized clinical trial of the effects of supplemental calcium and vitamin D3 on markers of their metabolism in normal mucosa of colorectal adenoma patients. Cancer Res. 2011;71:413–23.PubMedCrossRefGoogle Scholar
  20. 20.
    Peterlik M, Grant WB, Cross HS. Calcium, vitamin D and cancer. Anticancer Res. 2009;29:3687–98.PubMedGoogle Scholar
  21. 21.
    Whitfield JF. The calcium-sensing receptor – a driver of colon cell differentiation. Curr Pharm Biotechnol. 2009;10:311–6.PubMedCrossRefGoogle Scholar
  22. 22.
    Ghevariya V, Anand S. A short primer on the calcium sensing receptor: an important cog in the colon cancer wheel? Dig Dis Sci. 2011;56:279–84.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Barbara C. Pence
    • 1
  • Eric J. Belasco
    • 2
  • Conrad P. Lyford
    • 3
  1. 1.Department of PathologyTexas Tech University Health Sciences CenterLubbockUSA
  2. 2.Department of Agricultural Economics and EconomicsMontana State UniversityBozemanUSA
  3. 3.Department of Agricultural and Applied EconomicsTexas Tech UniversityLubbockUSA

Personalised recommendations