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Aspirin and Nonsteroidal Anti-inflammatory Drug Use and the Risk of Subsequent Colorectal Cancer

Aspirin and Nonsteroidal Anti-inflammatory Drug Use and the Risk of Subsequent Colorectal Cancer Abstract Objective: To test the hypothesis that the regular use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) is negatively associated with the risk of subsequent colorectal cancer. Design: Case-control study with four age- and sex-matched control subjects for each incident colorectal cancer case. Population and Setting: Patient population of a large municipal teaching hospital in Atlanta, Ga. Main Outcome Measure: Odds of colorectal cancer as a function of aspirin, nonaspirin NSAIDs, and acetaminophen dispensed to the study population in the 4 years prior to incident colorectal cancer diagnosis. Main Results: The risk of colorectal cancer estimated by odds ratios decreased with inceasing days of exposure to aspirin linearly in a dose-dependent fashion (likelihood ratio statistic: for cumulative days, P<.001; for cumulative dose, P<.0001). The coefficient for days of exposure to aspirin was highly significant even when modeled as a continuous variable (P=.001). There appeared to be a threshold above which nonaspirin NSAIDs afforded protection (likelihood ratio statistic: for cumulative days, P=.021; for cumulative dose, P=.019). Acetaminophen conferred no risk reduction. Conclusion: The results of previous experimental animal models, interventional case studies, and some but not all epidemiological investigations and the present data point toward a causal relationship between NSAID use and the prevention of cancer of the large bowel and rectum. Because of the potential gastrointestinal and renal side effects of NSAID use, particularly in the elderly, chemoprevention trials are now needed to allow riskbenefit analysis in populations at high risk for colorectal cancer.(Arch Intern Med. 1994;154:394-399) References 1. Marnett LJ. Aspirin and the potential role of prostaglandins in colon cancer . Cancer Res . 1992;52:5575-5589. 2. Narisawa T, Sato M, Tani M, Kudo T, Takahashi T, Goto A. Inhibition of development of methylnitrosourea-induced rat colon tumors by indomethacin treatment . Cancer Res . 1981;41:1954-1957. 3. Sato M, Narisawa T, Sano M, Takahasi T, Goto A. Growth inhibition of transplantable murine colon adenocarcinoma 38 by indomethacin . J Cancer Res Clin Oncol . 1983;106:21-26.Crossref 4. Pollard M, Luckert PH. Prolonged antitumor effect of indomethacin on autochronous intestinal tumors in rats . J Natl Cancer Inst . 1983;70:1103-1105. 5. Olson NO, Caignard A, Martin MS, Martin F. Effect of indomethacin on the growth of colon cancer cells in syngeneic rats . Int J Immunopharmacol . 1984;6:329-334.Crossref 6. Reddy BS, Maruyama H, Kelloff G. Dose-related inhibition of colon carcinogenesis by dietary piroxicam, a nonsteroidal anti-inflammatory drug, during different stages of colon tumor development . Cancer Res . 1987;47:5340-5346. 7. Skinner SA, Penney AG, O'Brien PE. Sulindac inhibits the rate of growth and appearance of colon tumors in the rat . Arch Surg . 1991;126:1094-1097.Crossref 8. Lynch NR, Cates M, Astoin M, Salomon JC. Mechanism of inhibition of tumour growth by aspirin and indomethacin . Br J Cancer . 1978;38:503-512.Crossref 9. Honn VK, Bockman RS, Marnett LJ. Prostaglandins and cancer: a review of tumor initiation thorough tumor metastasis . Prostaglandins . 1981;21:833-864.Crossref 10. Narisawa T, Kusaka H, Yamazaki Y, et al. Relationship between blood plasma prostaglandin E2 and liver and lung metastasis in colorectal cancer . Dis Colon Rectum . 1990;33:840-845.Crossref 11. Yamaguchi A, Ishida T, Nishimura G, Katoh M, Miyazaki I. Investigation of colonic prostaglandins in carcinogenesis in the rat colon . Dis Colon Rectum . 1991;34:572-576.Crossref 12. Flescher E, Fossum D, Gray PJ, et al. Aspirin-like drugs prime human T-cells . J Immunol . 1991;146:2553-2559. 13. Isomaki HA, Hakulinen T, Joutsenlahti U. Excess risk of lymphomas, leukemia and myeloma in patients with rheumatoid arthritis . J Chronic Dis . 1978;31:691-696.Crossref 14. Slavica K, Beard CM, Kurland LT, Weis JW, Bergstralh E. Occurrence of malignant neoplasms in the Rochester, Minnesota, rheumatoid arthritis cohort . Am J Med . 1985;78( (suppl 1A) ):50-55.Crossref 15. Gridley G, McLaughlin JK, Ekbom A, et al. Incidence of cancer among patients with rheumatoid arthritis . J Natl Cancer Inst . 1993;85:307-310.Crossref 16. Nicholls RJ, Springall RG, Gallagher P. Regression of rectal adenomas after colectomy and ileorectal anastomosis for familial adenomatous polyposis . BMJ . 1988;296:1707-1708.Crossref 17. Waddell WR, Ganser GF, Cerise EJ, Loughry RW. Sulindac for polyposis of the colon . Am J Surg . 1989;157:175-179.Crossref 18. Labayle D, Fischer D, Viehl P, et al. Sulindac causes regression of rectal polyps in familial adenomatous polyposis . Gastroenterology . 1991;101:635-639. 19. Rigau J, Pique JM, Rubio E, Planas R, Tarrech JM, Bordas JM. Effects of long-term sulindac therapy on colonic polyposis . Ann Intern Med . 1991;115:952-955.Crossref 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;48:4399-4404. 21. Rosenberg L, Palmer RJ, Zauber AG, Warshauer ME, Stolley PD, Shapiro S. A hypothesis: nonsteroidal anti-inflammatory drugs reduce the incidence of large-bowel cancer . J Natl Cancer Inst . 1991;83:355-358.Crossref 22. Suh O, Mettlin C, Petrelli NJ. Aspirin use, cancer, and polyps of the large bowel . Cancer . 1993;72:1171-1177.Crossref 23. Thun MJ, Namboodiri MM, Heath CW Jr. Aspirin use and reduced risk of fatal colon cancer . N Engl J Med . 1991;325:1593-1596.Crossref 24. Paganini-Hill A, Chao A, Ross RK, Henderson BE. Aspirin use and chronic diseases: a cohort study of the elderly . BMJ . 1989;299:1247-1250.Crossref 25. 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.Crossref 26. Walker HK, Camp H, Brown S. The Theresa on-line medical record . Read before the 14th Annual Meeting of the Society of General Internal Medicine; May 1, 1990; Seattle, Wash . 27. Statistical Application Software . Cary, NC: SAS Institute; 1992. 28. EGRET . Seattle, Wash: Statistics & Epidemiology Research Corp; 1992. 29. Paganini-Hill A, Hsu G, Ross RK, Henderson BE. Aspirin use and incidence of large-bowel cancer in a California retirement community . J Natl Cancer Inst . 1991;83:1182-1183.Crossref 30. Weisman G. Aspirin and aspirin-like drugs . In: Wyngaarden JB, Smith LH Jr, Bennett JT, eds. Cecil Textbook of Medicine . Philadelphia, Pa: WB Saunders Co; 1992:114-118. 31. Vane JR, Botting RM. The mode of action of anti-inflammatory drugs . Postgrad Med J . 1990;66:2-17. 32. Cyrer B, Feldman M. Effects of nonsteroidal anti-inflammatory drugs on endogenous gastrointestinal prostaglandins and therapeutic strategies for prevention and treatment of nonsteroidal anti-inflammatory drug-induced damage . Arch Intern Med . 1992;152:1145-1155.Crossref 33. Arrigoni-Martelli E. Drug treatment of inflammation: requirements and explanations . In: Bonta IL, Bray MA, Parnham MJ, eds. Handbook of Inflammation . New York, NY: Elsevier Science Publishers; 1985;5:1-25. 34. American Joint Committee on Cancer. Manual for Staging of Cancer . 3rd ed. Philadelphia, Pa: JB Lippincott; 1988. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

Aspirin and Nonsteroidal Anti-inflammatory Drug Use and the Risk of Subsequent Colorectal Cancer

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References (42)

Publisher
American Medical Association
Copyright
Copyright © 1994 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinte.1994.00420040050009
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Abstract

Abstract Objective: To test the hypothesis that the regular use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) is negatively associated with the risk of subsequent colorectal cancer. Design: Case-control study with four age- and sex-matched control subjects for each incident colorectal cancer case. Population and Setting: Patient population of a large municipal teaching hospital in Atlanta, Ga. Main Outcome Measure: Odds of colorectal cancer as a function of aspirin, nonaspirin NSAIDs, and acetaminophen dispensed to the study population in the 4 years prior to incident colorectal cancer diagnosis. Main Results: The risk of colorectal cancer estimated by odds ratios decreased with inceasing days of exposure to aspirin linearly in a dose-dependent fashion (likelihood ratio statistic: for cumulative days, P<.001; for cumulative dose, P<.0001). The coefficient for days of exposure to aspirin was highly significant even when modeled as a continuous variable (P=.001). There appeared to be a threshold above which nonaspirin NSAIDs afforded protection (likelihood ratio statistic: for cumulative days, P=.021; for cumulative dose, P=.019). Acetaminophen conferred no risk reduction. Conclusion: The results of previous experimental animal models, interventional case studies, and some but not all epidemiological investigations and the present data point toward a causal relationship between NSAID use and the prevention of cancer of the large bowel and rectum. Because of the potential gastrointestinal and renal side effects of NSAID use, particularly in the elderly, chemoprevention trials are now needed to allow riskbenefit analysis in populations at high risk for colorectal cancer.(Arch Intern Med. 1994;154:394-399) References 1. Marnett LJ. Aspirin and the potential role of prostaglandins in colon cancer . Cancer Res . 1992;52:5575-5589. 2. Narisawa T, Sato M, Tani M, Kudo T, Takahashi T, Goto A. Inhibition of development of methylnitrosourea-induced rat colon tumors by indomethacin treatment . Cancer Res . 1981;41:1954-1957. 3. Sato M, Narisawa T, Sano M, Takahasi T, Goto A. Growth inhibition of transplantable murine colon adenocarcinoma 38 by indomethacin . J Cancer Res Clin Oncol . 1983;106:21-26.Crossref 4. Pollard M, Luckert PH. Prolonged antitumor effect of indomethacin on autochronous intestinal tumors in rats . J Natl Cancer Inst . 1983;70:1103-1105. 5. Olson NO, Caignard A, Martin MS, Martin F. Effect of indomethacin on the growth of colon cancer cells in syngeneic rats . Int J Immunopharmacol . 1984;6:329-334.Crossref 6. Reddy BS, Maruyama H, Kelloff G. Dose-related inhibition of colon carcinogenesis by dietary piroxicam, a nonsteroidal anti-inflammatory drug, during different stages of colon tumor development . Cancer Res . 1987;47:5340-5346. 7. Skinner SA, Penney AG, O'Brien PE. Sulindac inhibits the rate of growth and appearance of colon tumors in the rat . Arch Surg . 1991;126:1094-1097.Crossref 8. Lynch NR, Cates M, Astoin M, Salomon JC. Mechanism of inhibition of tumour growth by aspirin and indomethacin . Br J Cancer . 1978;38:503-512.Crossref 9. Honn VK, Bockman RS, Marnett LJ. Prostaglandins and cancer: a review of tumor initiation thorough tumor metastasis . Prostaglandins . 1981;21:833-864.Crossref 10. Narisawa T, Kusaka H, Yamazaki Y, et al. Relationship between blood plasma prostaglandin E2 and liver and lung metastasis in colorectal cancer . Dis Colon Rectum . 1990;33:840-845.Crossref 11. Yamaguchi A, Ishida T, Nishimura G, Katoh M, Miyazaki I. Investigation of colonic prostaglandins in carcinogenesis in the rat colon . Dis Colon Rectum . 1991;34:572-576.Crossref 12. Flescher E, Fossum D, Gray PJ, et al. Aspirin-like drugs prime human T-cells . J Immunol . 1991;146:2553-2559. 13. Isomaki HA, Hakulinen T, Joutsenlahti U. Excess risk of lymphomas, leukemia and myeloma in patients with rheumatoid arthritis . J Chronic Dis . 1978;31:691-696.Crossref 14. Slavica K, Beard CM, Kurland LT, Weis JW, Bergstralh E. Occurrence of malignant neoplasms in the Rochester, Minnesota, rheumatoid arthritis cohort . Am J Med . 1985;78( (suppl 1A) ):50-55.Crossref 15. Gridley G, McLaughlin JK, Ekbom A, et al. Incidence of cancer among patients with rheumatoid arthritis . J Natl Cancer Inst . 1993;85:307-310.Crossref 16. Nicholls RJ, Springall RG, Gallagher P. Regression of rectal adenomas after colectomy and ileorectal anastomosis for familial adenomatous polyposis . BMJ . 1988;296:1707-1708.Crossref 17. Waddell WR, Ganser GF, Cerise EJ, Loughry RW. Sulindac for polyposis of the colon . Am J Surg . 1989;157:175-179.Crossref 18. Labayle D, Fischer D, Viehl P, et al. Sulindac causes regression of rectal polyps in familial adenomatous polyposis . Gastroenterology . 1991;101:635-639. 19. Rigau J, Pique JM, Rubio E, Planas R, Tarrech JM, Bordas JM. Effects of long-term sulindac therapy on colonic polyposis . Ann Intern Med . 1991;115:952-955.Crossref 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;48:4399-4404. 21. Rosenberg L, Palmer RJ, Zauber AG, Warshauer ME, Stolley PD, Shapiro S. A hypothesis: nonsteroidal anti-inflammatory drugs reduce the incidence of large-bowel cancer . J Natl Cancer Inst . 1991;83:355-358.Crossref 22. Suh O, Mettlin C, Petrelli NJ. Aspirin use, cancer, and polyps of the large bowel . Cancer . 1993;72:1171-1177.Crossref 23. Thun MJ, Namboodiri MM, Heath CW Jr. Aspirin use and reduced risk of fatal colon cancer . N Engl J Med . 1991;325:1593-1596.Crossref 24. Paganini-Hill A, Chao A, Ross RK, Henderson BE. Aspirin use and chronic diseases: a cohort study of the elderly . BMJ . 1989;299:1247-1250.Crossref 25. 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.Crossref 26. Walker HK, Camp H, Brown S. The Theresa on-line medical record . Read before the 14th Annual Meeting of the Society of General Internal Medicine; May 1, 1990; Seattle, Wash . 27. Statistical Application Software . Cary, NC: SAS Institute; 1992. 28. EGRET . Seattle, Wash: Statistics & Epidemiology Research Corp; 1992. 29. Paganini-Hill A, Hsu G, Ross RK, Henderson BE. Aspirin use and incidence of large-bowel cancer in a California retirement community . J Natl Cancer Inst . 1991;83:1182-1183.Crossref 30. Weisman G. Aspirin and aspirin-like drugs . In: Wyngaarden JB, Smith LH Jr, Bennett JT, eds. Cecil Textbook of Medicine . Philadelphia, Pa: WB Saunders Co; 1992:114-118. 31. Vane JR, Botting RM. The mode of action of anti-inflammatory drugs . Postgrad Med J . 1990;66:2-17. 32. Cyrer B, Feldman M. Effects of nonsteroidal anti-inflammatory drugs on endogenous gastrointestinal prostaglandins and therapeutic strategies for prevention and treatment of nonsteroidal anti-inflammatory drug-induced damage . Arch Intern Med . 1992;152:1145-1155.Crossref 33. Arrigoni-Martelli E. Drug treatment of inflammation: requirements and explanations . In: Bonta IL, Bray MA, Parnham MJ, eds. Handbook of Inflammation . New York, NY: Elsevier Science Publishers; 1985;5:1-25. 34. American Joint Committee on Cancer. Manual for Staging of Cancer . 3rd ed. Philadelphia, Pa: JB Lippincott; 1988.

Journal

Archives of Internal Medicine – American Medical Association

Published: Feb 28, 1994

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