Skip to main content
SpringerLink
Log in

NSAIDs and Gastrointestinal Cancer Prevention

  • Review Article
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Numerous studies report the relationship between aspirin and other nonsteroidal anti-inflammatories (NSAIDs) and cancer incidence, in particular for colorectal cancer. This paper systematically reviews the evidence of the effect of aspirin and other NSAIDs on the primary prevention of colorectal and other gastrointestinal cancers in the general population.

In 25 investigations of NSAIDs and colorectal cancer, 23 observational studies reported a relative risk reduction but estimates vary widely. Cohort studies generally indicate lesser reductions than case-control studies suggesting possible biases in the latter. Clear evidence of a dose relationship generally appears lacking but data do not indicate useful effects of aspirin in cardioprophylactic doses. Differences have otherwise not been detected between aspirin and other NSAIDs, nor between non-aspirin NSAIDs. There is some evidence that the risk of colorectal cancer reduces with increased duration of NSAID use. The lower incidence of oesophageal and gastric cancers results in smaller numbers of cases in the studies reporting these cancers, particularly in the cohort studies. The trend is for a risk reduction for oesophageal and gastric cancers in people taking NSAIDs, which is more likely to be statistically significant in the case-control studies. A very small number of observational studies have reported the relationship between NSAIDs and the incidence of pancreatic, gallbladder and liver cancers. These show no consistent relationship.

In view of the inadequate information about optimal dose and duration of NSAIDs for colorectal cancer reduction, and the adverse effects of NSAIDs, we are not yet in a position to recommend NSAIDs for the primary prevention of colorectal cancer in the general population.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II
Table III
Table IV

Similar content being viewed by others

References

  1. Office of National Statistics. Cancer trends in England and Wales 1950–1999. London: The Stationary Office, 2001

    Google Scholar 

  2. Winawer SJ, Zauber AG, O’Brien MJ, et al. Randomised comparison of surveillance intervals after colonoscopic removal of newly diagnosed adenomatous polyps. N Engl J Med 1993; 328: 901–6

    Article  PubMed  CAS  Google Scholar 

  3. Cairns A, Quirke P. Flat adenomas. Br J Surg 1999; 86: 1489–90

    Article  PubMed  CAS  Google Scholar 

  4. World Health Organization. IARC Handbook of Cancer Prevention. Non-steroidal anti-inflammatory drugs. Vol 1. Paris: International Agency for Research on Cancer, 1997

    Google Scholar 

  5. Arber N. Do NSAIDs prevent colorectal cancer? Can J Gastroenterol 2000; 14: 299–307

    PubMed  CAS  Google Scholar 

  6. NHS Centre for Reviews and Dissemination. Undertaking systematic reviews of research on effectiveness. CRD Report Number 4. 2nd ed. York: University of York, 2001

    Google Scholar 

  7. Isomaki HA, Hakulinen T, Kannan K. Excess risk of lymphoma, leukemia and myeloma in patients with rheumatoid arthritis. J Chronic Dis 1978; 31: 691–6

    Article  PubMed  CAS  Google Scholar 

  8. Gridley G, McLaughlin JK, Ekbom A, et al. Incidence of cancer among patients with rheumatoid arthritis. J Natl Cancer Inst 1993; 85: 307–11

    Article  PubMed  CAS  Google Scholar 

  9. Paganini-Hill A. Aspirin use and chronic diseases: a cohort study of the elderly. BMJ 1989; 299: 1247–50

    Article  PubMed  CAS  Google Scholar 

  10. Paganini-Hill A, Hsu G, Ross RK, et al. Aspirin use and incidence of large bowel cancer in a California retirement. J Natl Cancer Inst 1991; 83: 1182–3

    Article  PubMed  CAS  Google Scholar 

  11. Paganini-Hill A. Aspirin and colorectal cancer: the Leisure World Cohort revisited. Prev Med 1995; 24: 113–5

    Article  PubMed  CAS  Google Scholar 

  12. Thun MJ. Aspirin use and risk of fatal cancer. Cancer Res 1993; 53: 1322–7

    PubMed  CAS  Google Scholar 

  13. Schreinemachers DM, Everson RB. Aspirin use and lung, colon and breast cancer incidence in a prospective study. Epidemiology 1994; 5: 138–46

    Article  PubMed  CAS  Google Scholar 

  14. Giovannucci E, Rimm EG, Stampfer KM, et al. Aspirin use and the risk for colorectal cancer and adenoma in male health professionals. Ann Intern Med 1994; 121: 241–6

    PubMed  CAS  Google Scholar 

  15. Giovannucci E, Egan KM, Hunter DJ, et al. Aspirin and the risk of colorectal cancer in women. N Engl J Med 1995; 333: 609–14

    Article  PubMed  CAS  Google Scholar 

  16. Kauppi M, Pukkala E, Isomaki H. Low incidence of colorectal cancer in patients with rheumatoid arthritis. Clin Exp Rheumatol 1996; 14: 551–3

    PubMed  CAS  Google Scholar 

  17. Cibere J, Sibley J, Haga M. Rheumatoid arthritis and the risk of malignancy. Arthritis Rheum 1997; 40: 1580–6

    Article  PubMed  CAS  Google Scholar 

  18. Smalley W, Ray WA, Daugherty J, et al. Use of nonsteroidal anti-inflammatory drugs and incidence of colorectal cancer. Arch Intern Med 1999; 159: 161–6

    Article  PubMed  CAS  Google Scholar 

  19. Bucher C, Jordan P, Nickeleit V, et al. Relative risk of malignant tumors in analgesic abusers: effects of long-term intake of aspirin. Clin Nephrol 1999; 51: 67–72

    PubMed  CAS  Google Scholar 

  20. Kune GA, Kune S, Watson LF. Colorectal cancer risk, chronic illnesses, operations, and medications: case-control results from the Melbourne Colorectal Cancer Study. Cancer Res 1988; 48: 4399–404

    PubMed  CAS  Google Scholar 

  21. Rosenberg L, Palmer JR, Zauber AG, et al. A hypothesis: nonsteroidal anti-inflammatory drugs reduce the incidence of large-bowel cancer. J Natl Cancer Inst 1991; 83: 355–8

    Article  PubMed  CAS  Google Scholar 

  22. Suh O, Mettlin C, Petrelli NJ. Aspirin use, cancer, and polyps of the large bowel. Cancer 1993; 72: 1171–7

    Article  PubMed  CAS  Google Scholar 

  23. Peleg I, Maibach HT, Brown SH, et al. Aspirin and nonsteroidal anti-inflammatory drug use and the risk of subsequent colorectal cancer. Arch Intern Med 1994; 154: 394–9

    Article  PubMed  CAS  Google Scholar 

  24. Muscat JE, Stellman SD, Wynder EL. Non-steroidal anti-inflammatory drugs and colorectal cancer. Cancer 1994; 74: 1847–54

    Article  PubMed  CAS  Google Scholar 

  25. Muller AD, Sonnenberg A, Wasserman IH. Diseases preceding colon cancer: a case-control study among veterans. Dig Dis Sci 1994; 39: 2480–4

    Article  PubMed  CAS  Google Scholar 

  26. Reeves MJ, Newcombe PA, Trentham-Dietz A, et al. Non-steroidal anti-inflammatory drug use and protection against colorectal cancer in women. Cancer Epidemiol Biomarkers Prev 1996; 5: 955–60

    PubMed  CAS  Google Scholar 

  27. Bansal P, Sonnenberg A. Risk factors of colorectal cancer in inflammatory bowel disease. Am J Gastroenterol 1996; 91: 44–8

    PubMed  CAS  Google Scholar 

  28. Peleg II, Lubin MF, Cotsonis GA, et al. Long-term use of nonsteroidal anti-inflammatory drugs and other chemopreventors and risk of subsequent colorectal neoplasia. Dig Dis Sci 1996; 41: 1319–6

    Article  PubMed  CAS  Google Scholar 

  29. La Vecchia C, Negri E, Franceschi S, et al. Aspirin and colorectal cancer. Br J Cancer 1997; 76: 675–7

    Article  PubMed  Google Scholar 

  30. Rosenberg L, Louik C, Shapiro S. Nonsteroidal anti-inflammatory drug use and reduced risk of large bowel cancer. Cancer 1998; 83: 2326–33

    Article  Google Scholar 

  31. Collett JP, Sharpe C, Belzile E, et al. Colorectal cancer prevention by non-steroidal anti-inflammatory drugs: effects of dosage and timing. Br J Cancer 1999; 81: 62–8

    Article  Google Scholar 

  32. Langman MJS, Cheng KK, Gilman A, et al. Effect of anti-inflammatory drugs on overall risk of common cancer: case-control study in general practice research database. BMJ 2000; 320: 1642–6

    Article  PubMed  CAS  Google Scholar 

  33. Garcia Rodriguez LA, Huerta-Alvarez C. Reduced risk of colorectal cancer among long-term users of aspirin and non-aspirin non-steroidal antiinflammatory drugs. Epidemiology 2001; 12: 88–93

    Article  PubMed  CAS  Google Scholar 

  34. Gann PH, Manson JE, Glunn RJ, et al. Low dose aspirin and incidence of colorectal tumors in randomised trial. J Natl Cancer Inst 1993; 85: 1220–4

    Article  PubMed  CAS  Google Scholar 

  35. Sturmer T, Glynn RJ, Lee IM, et al. Aspirin use and colorectal cancer: post-trial follow-up data from the Physicians’ Health Study. Ann Intern Med 1998; 128: 713–20

    PubMed  CAS  Google Scholar 

  36. Funkhauser EM, Sharp GB. Aspirin and reduced risk of esophageal carcinoma. Cancer 1995; 76: 1116–9

    Article  Google Scholar 

  37. Farrow DC, Vaughan TL, Hansten PD, et al. Use of aspirin and other nonsteroidal anti-inflammatory drugs and risk of esophageal and gastric cancer. Cancer Epidemiol Biomarkers Prev 1998; 7: 97–102

    PubMed  CAS  Google Scholar 

  38. Coogan PF, Rosenberg L, Palmer JR, et al. Nonsteroidal anti-inflammatory drugs and risk of digestive cancers at sites other than the large bowel. Cancer Epidemiol Biomarkers Prev 2000; 9: 119–23

    PubMed  CAS  Google Scholar 

  39. Zaridze D, Borisova E, Maximovitch D, et al. Aspirin protects against gastric cancer: results of a case-control study from Moscow, Russia. Int J Cancer 1999; 82: 473–6

    Article  PubMed  CAS  Google Scholar 

  40. Akre K, Ekstrom AM, Signorello LB, et al. Aspirin and risk for gastric cancer: a population-based case-control study in Sweden. Br J Cancer 2001; 84(7): 965–8

    Article  PubMed  CAS  Google Scholar 

  41. Garidou A, Tzonou A, Lipworth L, et al. Life-style factors and medical conditions in relation to esophageal cancer by histologic type in a low-risk population. Int J Cancer 1996; 68: 295–9

    Article  PubMed  CAS  Google Scholar 

  42. Logan RF, Little J, Hawtin PG, et al. Effect of aspirin and nonsteroidal anti-inflammatory drugs on colorectal ademonas: case-control study of subjects participating in the Nottingham faecal occult blood screening programme. BMJ 1993; 307: 285–9

    Article  PubMed  CAS  Google Scholar 

  43. Martinez ME, McPherson RS, Levin B, et al. Aspirin and other nonsteroidal anti-inflammatory drugs and risk of colorectal adenomatous polyps among endoscoped individuals. Cancer Epidemiol Biomarkers Prev 1995; 4: 703–7

    PubMed  CAS  Google Scholar 

  44. Yang VW, Shields JM, Hamilton SR, et al. Size-dependent increase in prosanoid levels in adenomas of patients with familial adenomatous polyposis. Cancer Res 1998; 58: 1750–3

    PubMed  CAS  Google Scholar 

  45. Kudo T, Narisawa T, Abo S. Antitumor activity of indomethacin on methyloxymethanol-induced large bowel tumors in rats. Gann 1980; 71: 260–4

    PubMed  CAS  Google Scholar 

  46. Beazer-Barclay Y, Levy DB, Moser AR, et al. Sulindac suppresses tumorigenesis in the Min mouse. Carcinogenesis 1996; 17: 1757–60

    Article  PubMed  CAS  Google Scholar 

  47. Boolbol SK, Dannenberg AJ, Chadburn A, et al. Cyclooxygenase-2 over-expression and tumor formation are blocked by sulindac in a murine model of familial adenomatous polyposis. Cancer Res 1996; 56: 2556–60

    PubMed  CAS  Google Scholar 

  48. Jacoby RF, Marshall DJ, Newton MA, et al. Chemoprevention of spontaneous intestinal adenomas in the Apc Min mouse model by the nonsteroidal anti-inflammatory drug piroxicam. Cancer Res 1996; 56: 710–4

    PubMed  CAS  Google Scholar 

  49. Schiff SJ, Rigas B. Non-steroidal anti-inflammatory drugs and colorectal cancer: evolving concepts of their chemopreventive actions. Gastroenterology 1997; 113: 1992–8

    Article  Google Scholar 

  50. Piazza GA, Rahm AL, Krutzsch M, et al. Antineoplastic drugs sulindac sulphide and sulphone inhibit cell growth by inducing apoptosis. Cancer Res 1995; 55: 3110–6

    PubMed  CAS  Google Scholar 

  51. Piazza GA, Rahm AK, Finn TS, et al. Apoptosis primarily accounts for the growth-inhibitory properties of sulindac metabolites and involves a mechanism that is independent of cyclooxygenase inhibition, cell cycle arrest, and p53 induction. Cancer Res 1997; 57: 2452–9

    PubMed  CAS  Google Scholar 

  52. Li M, Lotan R, Levin B, et al. Aspirin induction of apoptosis in esophageal cancer: a potential for chemoprevention. Cancer Epidemiol Biomarkers Prev 2000; 9: 545–9

    PubMed  CAS  Google Scholar 

  53. Molina MA, Sitja-Arnau M, Lemoine MG, et al. Increased cyclooxygenase-2 expression in human pancreatic carcinomas and cell lines: growth inhibition by nonsteroidal anti-inflammatory drugs. Cancer Res 1999; 59: 4356–62

    PubMed  CAS  Google Scholar 

  54. Morgan G, Vainio H. Barrett’s oesophagus, oesophageal cancer and colon cancer; an explanation of the association and cancer chemopreventive potential of non-steroidal anti-inflammatory drugs. Eur J Cancer Prev 1998; 7: 195–9

    Article  PubMed  CAS  Google Scholar 

  55. Li M, Wu X, Xu XC. Induction of apoptosis by cyclo-oxygenase-2 inhibitor NS398 through a cytochrome-c dependent pathway in esophageal cancer cells. Int J Cancer 2001; 93: 218–23

    Article  PubMed  CAS  Google Scholar 

  56. Labayle D, Fischer D, Vielh P, et al. Sulindac causes regression of rectal polyps in familial adenosis polyposis. Gastroenterology 1991; 101: 635–9

    PubMed  CAS  Google Scholar 

  57. Giardiello FM, Hamilton SR, Krush AJ, et al. Treatment of colonic and rectal adenomas with sulindac in familial adenosis polyposis. N Engl J Med 1993; 328: 1313–6

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

Professor Langman has acted as a consultant for Merck Sharp and Dohme. Any payment received goes to the University of Birmingham.

Author information

Authors and Affiliations

  1. Department of Public Health and Epidemiology, University of Birmingham, Edgbaston, B15 2TT, Birmingham, UK

    Kate Jolly &  Kar K. Cheng

  2. Department of Medicine, University of Birmingham, Birmingham, UK

    Michael J. S. Langman

Authors
  1. Kate Jolly
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kar K. Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael J. S. Langman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kar K. Cheng.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jolly, K., Cheng, K.K. & Langman, M.J.S. NSAIDs and Gastrointestinal Cancer Prevention. Drugs 62, 945–956 (2002). https://doi.org/10.2165/00003495-200262060-00006

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-200262060-00006

Keywords

Search

Navigation