Cancer Causes & Control

, Volume 14, Issue 5, pp 403–411 | Cite as

Non-steroidal anti-inflammatory drug use is associated with reduction in recurrence of advanced and non-advanced colorectal adenomas (United States)

  • Joseph A. TangreaEmail author
  • Paul S. Albert
  • Elaine Lanza
  • Karen Woodson
  • Don Corle
  • Marsha Hasson
  • Randall Burt
  • Bette Caan
  • Electra Paskett
  • Frank Iber
  • J. Walter Kikendall
  • Peter Lance
  • Moshe Shike
  • Joel Weissfeld
  • Arthur Schatzkin


Objective: To prospectively examine the association between non-steroidal anti-inflammatory drugs (NSAIDs) use (including dose and dosage schedule) and the recurrence of colorectal adenomas among individuals who were diagnosed with an adenoma at entry into a clinical trial. Methods: For this analysis, participants who completed the full follow-up (n = 1905) for the Polyp Prevention Trial (PPT) were evaluated. Information on current use and dose of NSAIDs and other drugs was obtained at baseline and at each subsequent study visit over the duration of the trial. The study endpoint was the recurrence of colorectal adenomas in the 3 years between the 1-year trial colonoscopy (T1) and the end of the trial colonoscopy (T4). Results: There was a significant reduction in overall adenoma recurrence among NSAIDs users (odds ratio [OR] = 0.77; 95% confidence interval [CI]: 0.63–0.95), with the greatest effect seen in advanced polyps (OR = 0.51; CI: 0.33–0.79). Among aspirin users, we observed a significant dose response for overall adenoma recurrence, with a 40% reduction in the OR association (OR = 0.56; 95% CI: 0.31–0.99) among those taking more than 325 mg per day. Conclusion: This prospective study provides further evidence that NSAIDs may play an important role in the chemoprevention of recurrent colorectal adenomas, even those with advanced features.

adenomas non-steroidal anti-inflammatory drugs prospective risk 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Garcia Rodriguez LA, Huerta-Alvarez C (2000) Reduced incidence of colorectal adenoma among long-term users of nonsteroidal antiinflammatory drugs: a pooled analysis of published studies and a new population-based study. Epidemiology 11: 376-381.Google Scholar
  2. 2.
    Weiss HA, Forman D (1996) Aspirin, non-steroidal anti-inflammatory drugs and protection from colorectal cancer: a review of the epidemiological evidence. Scand J Gastroenterol 31(Suppl. 220): 137-141.Google Scholar
  3. 3.
    Baron JA, Sandier RS (2000) Nonsteroidal anti-inflammatory drugs and cancer prevention. Ann Rev Med 51: 511-523.Google Scholar
  4. 4.
    Strausser HR, Humes JL (1975) Prostaglandin synthesis inhibition: effect on bone changes and sarcoma tumor induction in BALB/c mice. Cancer 15: 724-730.Google Scholar
  5. 5.
    Hial V, Horakova Z, Shaff RE, Beaven MA (1976) Alteration of tumor growth by aspirin and indomethacin: studies with two transplantable tumors in mouse. Eur J Pharmacol 37: 367-376.Google Scholar
  6. 6.
    Lynch NR, Castes M, Astoin M, Salomon JC (1978) Mechanism of inhibition of tumor growth by aspirin and indomethacin. Br J Cancer 38: 503-512.Google Scholar
  7. 7.
    Lynch NR, Salomon JC (1979) Tumor growth inhibition and potentiation of immunotherapy by indomethacin in mice. J Natl Cancer Inst 62: 117-121.Google Scholar
  8. 8.
    Waddell WR, Loughry RW (1983) Sulindac for polyposis of the colon. J Surg Oncol 24: 83-87.Google Scholar
  9. 9.
    Labayle D, Fischer D, Vielh P, et al. (1991) Sulindac causes regression of rectal polyps in familial adenomatous polyposis. Gastroenterology 101: 635-639.Google Scholar
  10. 10.
    Rigau J, Pique JM, Rubio E, Planas R, Tarrech JM, Bordas JM (1991) Effect of long-term sulindac on colonic polyposis. Ann Intern Med 115: 952-954.Google Scholar
  11. 11.
    Giardiello FM, Hamilton SR, Krush AJ, et al. (1993) Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. N Engl Med 328: 1313-1316.Google Scholar
  12. 12.
    Nugent KP, Farmer KG, Spigelman AD, Williams CB, Phillips RK (1993) Randomized controlled trial of the effect of sulindac on duodenal and rectal polyposis and cell proliferation in patients with familial adenomatous polyposis. Br J Surg 80: 1618-1619.Google Scholar
  13. 13.
    Spagnesi MT, Tonelli F, Dolara P, et al. (1994) Rectal proliferation and polyp occurrence in patients with familial adenomatous polyposis. Gastroenterology 106: 362-366.Google Scholar
  14. 14.
    Winde G, Schmid KW, Schlegel W, Fischer R, Osswald H, Bunte H (1995) Complete reversion and prevention of rectal adenomas in colectomized patients with familial adenomatous polyposis by rectal low dose sulindac maintenance treatment. Dis Colon Rectum 38: 813-830.Google Scholar
  15. 15.
    Rosenberg L, Palmer JR, Zauber AG, Warshauer ME, Stolley PD, Shapiro S (1991) A hypothesis: nonsteroidal anti-inflammatory drugs reduce the incidence of large bowel cancer. J Natl Cancer Inst 83: 355-358.Google Scholar
  16. 16.
    Thun MJ, Namboodiri MM, Heath CW (1991) Aspirin use and reduced risk of fatal colon cancer. N Engl J Med 325: 1593-1596.Google Scholar
  17. 17.
    Suh O, Mettlin C, Petrelli NJ (1993) Aspirin use, cancer and polyps of the large bowel. Cancer 72: 1171-1177.Google Scholar
  18. 18.
    Logan RF, Little J, Hawtin PG, Hardcastle JD (1993) Effect of aspirin and non-steroidal anti-inflammatory drugs on colorectal adenomas: case-control study of subjects participating in the Nottingham faecal occult blood screening programme. Br Med J 307: 285-289.Google Scholar
  19. 19.
    Greenberg ER, Baron JA, Freeman DH, Mandel JS, Haile R for the Polyp Prevention Study Group (1993) Reduced risk for large bowel adenomas among aspirin users. J Natl Cancer Inst 85: 912-916.Google Scholar
  20. 20.
    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: 1220-1224.Google Scholar
  21. 21.
    Giovannucci E, Rimm EB, Stampfer MJ, Colditz GA, Ascherio A, Willett WC (1994) Aspirin use and the risk for colorectal cancer and adenoma in male health professionals. Ann Int Med 121: 241-246.Google Scholar
  22. 22.
    Muscat JE, Stellman SD, Wynder EL (1994) Nonsteroidal antiinflammatory drugs and colorectal cancer. Cancer 74: 1847-1854.Google Scholar
  23. 23.
    Martinez ME, McPherson RS, Levin B, Annegers JF (1995) Aspirin and other nonsteroidal anti-inflammatory drugs and risk of colorectal adenomatous polyps among endoscoped individuals. Cancer Epidemiol Biomarkers Prev 4: 703-707.Google Scholar
  24. 24.
    Peleg II, Lubin MF, Cotsonis GA, Clark WS, Wilcox CM (1996) Long-term use of nonsteroidal antiinflammatory drugs and other chemopreventors and risk of subsequent colorectal neoplasia. Dig Dis Sci 41: 1319-1326.Google Scholar
  25. 25.
    Sandier RA, Galanko JC, Murray SC, Helm SJ, Woosley JT (1998) Aspirin and nonsteroidal anti-inflammatory agents and risk for colorectal adenomas. Gastroenterology 114: 441-447.Google Scholar
  26. 26.
    Smalley W, Ray WA, Daugherty J, Griffin MR (1999) Use of nonsteroidal anti-inflammatory drugs and incidence of colorectal cancer. Arch Intern Med 159: 161-166.Google Scholar
  27. 27.
    Arber N, DuBois RN (1999) Nonsteroidal anti-inflammatory drugs and prevention of colorectal cancer. Curr Gastroenterol Rep 1: 441-448.Google Scholar
  28. 28.
    Breuer-Katschinski B, Nemes K, Rump B, et al. and The Colorectal Adenoma Study Group (2000) Long-term use of nonsteroidal antiinflammatory drugs and the risk of colorectal adenomas. Digestion 61: 129-134.Google Scholar
  29. 29.
    Coogan PF, Rosenberg L, Louik C, et al. (2000) NSAIDs and risk of colorectal cancer according to presence or absence of family history of disease. Cancer Causes Control 11: 249-255.Google Scholar
  30. 30.
    Rodriguez LAG, Huerta-Alvarez C (2001) Reduced risk of colorectal cancer among long-term users of aspirin and nonaspirin nonsteroidal antiinflammatory drugs. Epidemiology 12: 88-93.Google Scholar
  31. 31.
    Schatzkin A, Lanza E, Freedman LS, et al. (1996) The polyp prevention trial I: rationale, design, recruitment, and baseline participant characteristics. Cancer Epidemiol Biomarkers Prev 5: 375-383.Google Scholar
  32. 32.
    Lanza E, Schatzkin A, Ballard-Barbash R, et al. (1996) The polyp prevention trial II: dietary intervention program and participant baseline dietary characteristics. Cancer Epidemiol Biomarkers Prev 5: 385-392.Google Scholar
  33. 33.
    Schatzkin A, Lanza E, Corle D, et al. and the Polyp Prevention Trial Group (2000) Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal adenomas. N Engl J Med 342: 1149-1155.Google Scholar
  34. 34.
    American Hospital Formulary Service Drug Information (2000) In: McEvoy G., ed. Bethesda, MD: American Society of Health System Pharmacists, 2000.Google Scholar
  35. 35.
    Zhang J, Yu KF (1998) What's the relative risk? A method of correcting the odds ratios in cohort studies of common outcomes. JAMA 280: 1690-1691.Google Scholar
  36. 36.
    Richter M, Weiss M, Weinberger I, Fursternberger G, Marian B (2001) Growth inhibition and induction of apoptosis in colorectal tumor cells by cyclooxygenase inhibitors. Carcinogenesis 22: 17-25.Google Scholar
  37. 37.
    Hixson LJ, Earnest DL, Fennerty MB, Sampliner RE (1993) NSAID effect on sporadic colon polyps. Am J Gastroenterol 88: 1652-1656.Google Scholar
  38. 38.
    Ladenheim J, Garcia G, Titzer D, et al. (1995) Effect of sulindac on sporadic colonic polyps. Gastroenterology 108: 1083-1087.Google Scholar
  39. 39.
    Matsuhashi N, Nakajima A, Fukushima Y, Yazaki Y, Oka T (1997) Effects of sulindac on sporadic colorectal adenomatous polyps. Gut 40: 344-349.Google Scholar

Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • Joseph A. Tangrea
    • 1
    Email author
  • Paul S. Albert
    • 2
  • Elaine Lanza
    • 3
  • Karen Woodson
    • 3
  • Don Corle
    • 4
  • Marsha Hasson
    • 5
  • Randall Burt
    • 6
  • Bette Caan
    • 7
  • Electra Paskett
    • 8
  • Frank Iber
    • 9
  • J. Walter Kikendall
    • 10
  • Peter Lance
    • 11
  • Moshe Shike
    • 12
  • Joel Weissfeld
    • 13
  • Arthur Schatzkin
    • 14
  1. 1.Center for Cancer Research, Cancer Prevention Studies BranchNational Cancer InstituteBethesdaUSA
  2. 2.Biometric Research Branch, Division of Cancer Treatment and DiagnosisNational Cancer InstituteBethesdaUSA
  3. 3.Cancer Prevention Studies Branch, Center for Cancer ResearchNational Cancer InstituteBethesdaUSA
  4. 4.Biometry Research Group, Division of Cancer PreventionNational Cancer InstituteBethesdaUSA
  5. 5.WestatRockvilleUSA
  6. 6.University of UtahSalt Lake CityUSA
  7. 7.Kaiser Foundation Research InstituteOaklandUSA
  8. 8.Wake Forest University School of MedicineWinston-SalemUSA
  9. 9.Edward Hines, Jr, HospitalVeterans Affairs Medical CenterHinesUSA
  10. 10.Walter Reed Army Medical CenterWashington, DCUSA
  11. 11.School of Medicine and Biomedical SciencesState University of New York at BuffaloBuffaloUSA
  12. 12.Memorial Sloan-Kettering Cancer CenterNew YorkUSA
  13. 13.University of PittsburghPittsburghUSA
  14. 14.Nutritional Epidemiology Branch, Division of Epidemiology and GeneticsNational Cancer InstituteBethesdaUSA

Personalised recommendations