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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 400))

Abstract

In rodents, nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin inhibit chemically induced adenomas and early carcinomas of the colon. The NSAID Sulindac inhibits the growth of polyps of the colon and rectum in two randomized trials of patients with familial adenomatous polyposis (FAP), although the inhibition is not complete. Eight epidemiologic studies have found a 40–50% reduction in polyps or colorectal cancer among persons who regularly use aspirin or other NSAIDs compared to those who do not. Two epidemiologic studies show a slight increase in risk. Interpretation of the epidemiologic studies is complicated, because bleeding induced by aspirin may enhance the diagnosis and early treatment of cancer, and at least in theory, the symptoms of cancer could cause patients to avoid aspirin. Clinical trials designed specifically to investigate the aspirin hypothesis in humans at high risk of colorectal polyps or cancer are needed to establish causality, and to define the optimal dose and drug. Experimental studies should further define the mechanism of tumor inhibition in animals.

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References

  1. Marnett, L.J. Aspirin and the role of prostaglandins in cancer. Cancer Res 52:5575–5589, 1992.

    CAS  Google Scholar 

  2. Pollard, M. and Luckert, P.H. Indomethacin treatment of rats with dimethylhydrazine-induced intestinal tumors. Cancer Treat Rep 64:1323–1327, 1980.

    CAS  Google Scholar 

  3. Kudo, T., Narisawa, T. and Abo, S. Antitumor activity of indomethacin on methylazoxymethanol-induced large bowel tumors in rats. Gann 71:260–264, 1980.

    CAS  Google Scholar 

  4. Pollard, M. and Luckert, P.H. Effect of indomethacin on intestinal tumors induced in rats by the acetate derivative of dimethylnitrosamine. Science 214:558–559, 1981.

    CAS  Google Scholar 

  5. Pollard, M. and Luckert, PH. Treatment of chemically-induced intestinal cancers with indomethacin. Proc Soc Exp Biol Med 167:161–164, 1981.

    CAS  Google Scholar 

  6. Narisawa, T., Sato, M., Tani, M., Kudo, T., Takahashi, T. and Goto, A. Inhibition of development of methylnitrosourea-induced rat colon tumors by indomethacin treatment. Cancer Res 41:1954–1957, 1981.

    CAS  Google Scholar 

  7. Pollard, M., Luckert, P.H. and Schmidt, M.A. The suppressive effect of piroxicam on autochthonous intestinal tumors in the rat. Cancer Lett 21:57–61, 1983.

    CAS  Google Scholar 

  8. Pollard, M. and Luckert, P.H. Prolonged antitumor effect of indomethacin on autochthonous intestinal tumors in rats. J Natl Cancer Inst 70:1103–1105, 1983.

    CAS  Google Scholar 

  9. Narisawa, T., Satoh, M, Sano, M. and Takahashi, T. Inhibition of initiation and promotion by N-methylnitrosourea-induced colon carcinogenesis in rats by non-steroid anti-inflammatory agent indomethacin. Carcinogenesis 4:1225–1227, 1983.

    CAS  Google Scholar 

  10. Pollard, M. and Luckert, P.H. Effect of piroxicam on primary intestinal tumors induced in rats by N-methylnitrosourea. Cancer Lett 25:117–121, 1984.

    CAS  Google Scholar 

  11. Narisawa, T., Hermanek, P., Habs, M. and Schmahl, D. Reduction of carcinogenicity of N-Nitrosomethylurea by indomethacin and failure of resuming effect of Prostaglandin E2 (PGE2) against indomethacin. J Cancer Res Clin Oncol 108:239–242, 1984.

    Article  PubMed  CAS  Google Scholar 

  12. Metzger, U., Meier, J., Uhlschmid, G. and Weihe, H. Influence of various prostaglandin synthesis inhibitors on DMH-induced rat colon cancer. Dis Colon Rectum 27:366–369, 1984.

    CAS  Google Scholar 

  13. Pollard, M. Antitumor effect of indomethacin in rats with autochthonous intestinal tumors. In Frontiers in Gastrointestinal cancer (Levin B, Riddell RH, eds.). New York: Elsevier, pp. 91–103, 1984.

    Google Scholar 

  14. Nigro, D.N., Bull, A.W. and Boyd, M.E. Inhibition of intestinal carcinogenesis in rats: effect of difluoromethylornithine with piroxicam or fish oil. J Natl Cancer Inst 77:1309–1313, 1986.

    PubMed  CAS  Google Scholar 

  15. Reddy, B.S., Maruyama, H. and Kelloff, G. Dose-related inhibition of colon carcinogenesis by dietary piroxicam, a nonsteroidal anti-inflammatory drug, during different stages of rat colon tumor development. Cancer Res 47:5340–5346, 1987.

    PubMed  CAS  Google Scholar 

  16. Moorghen, M., Ince, P., Finney, K., Sunter, J.P., Appleton, D.R. and Watson, A.J. A protective effect of sulindac against chemically-induced primary colonic tumors in mice. Journal of Path 156:341–347, 1988.

    CAS  Google Scholar 

  17. Pollard, M. and Luckert, P.H. Prevention and treatment of primary intestinal tumors in rats by piroxicam. Cancer Res 49:6471–6473, 1989.

    CAS  Google Scholar 

  18. Rubio, C.A., Wallin, B., Ware, J., Sveander, M. and Duvander, A. Effect of indomethacin in autotransplanted colonic tumors. Dis Colon Rectum 32:488–491, 1989.

    CAS  Google Scholar 

  19. Reddy, B.S., Nayini, J., Tokumo, K., Rigotty, J., Zang, E. and Kelloff, G. Chemoprevention of colon carcinogenesis by concurrent administration of piroxicam, a nonsteroidal anti-inflammatory drug with D,L,—difluromethylornithine, an ornithine decarboxylase inhibitor, in diet. Cancer Res 50:2562–2568, 1990.

    CAS  Google Scholar 

  20. Rao, C.V., Tokumo, K., Rigotty, J., Zang, E., Kelloff, G. and Reddy, B.S. Chemoprevention of colon carcinogenesis by dietary administration of piroxicam,-difluoromethylornithine, 16-fluoro-5-androsten-17-one, and ellagic acid individually and in combination. Cancer Res 51:4528–4534, 1991.

    PubMed  CAS  Google Scholar 

  21. Skinner, S.A., Penney, A.G. and O’Brian, P.E. Sulindac inhibits the rate of growth and appearance of colon tumors in the rat. Arch Surg 126:1094–1096, 1991.

    Article  PubMed  CAS  Google Scholar 

  22. Craven, P.A. and Derubertis, F.R. Effects of aspirin on 1,-dimethylhydrazine-induced colonie carcinogenesis. Carcinogenesis 13:541–546, 1992.

    CAS  Google Scholar 

  23. Labayle, D., Fischer, D. and Vielh, P. et al. Sulindac causes regression of rectal polyps in familial adenomatous polyposis. Gastroenterology 101:635–639, 1991.

    CAS  Google Scholar 

  24. Giardiello, F.M., Hamilton, S.R. and Krush, A.J. et al. Treatment of colonie and rectal adenomas with sulindac in familial adenomatous polyposis. N Eng J Med 328:1313–1316, 1993.

    CAS  Google Scholar 

  25. Kune, G., Kune, S. and Watson, L. Colorectal cancer risk, chronic illnesses, operations, and medications: case control results from the Melborne Colorectal Cancer Study. Cancer Res 48:4399–4404, 1988.

    PubMed  CAS  Google Scholar 

  26. Paganini-Hill, A., Chao, A, Ross, R.K. and Henderson, B.E. Aspirin use and chronic diseases: a cohort study of the elderly. BMJ 229:1247–1250, 1989.

    Google Scholar 

  27. Rosenberg, L., Palmer, J.R., Zauber, A.G., Warshauer, M.E., Stolley, P.D. and Shapiro, S. A Hypothesis: Nonsteroidal anti-inflammatory drugs reduce the incidence of large-bowel cancer. J Natl Cancer Inst 83:355–358, 1991.

    CAS  Google Scholar 

  28. Thun, M., Namboodiri, M. and Heath, C. Aspirin use and reduced risk of fatal colon cancer. N Engl J Med 325:1593–1596, 1991.

    CAS  Google Scholar 

  29. Thun, M., Namboodiri, M., Calle, E.E., Flanders, W.D. and Heath, C.W. Aspirin use and risk of fatal cancer. Cancer Res 53:1322–1327, 1993.

    CAS  Google Scholar 

  30. Gridley, G., McLaughlin, J.K., Ekbom A., et al. Incidence of cancer among patients with rheumatoid arthritis. J Natl Cancer Instit 85,307–311, 1993.

    Article  CAS  Google Scholar 

  31. Isomaki, H.A., Hakulinen, T. and Joutsenlahti, U. Excess risk of lymphomas, leukemia, and myeloma in patients with rheumatoid arthritis. J Chron Dis 31:691–696, 1978.

    Article  PubMed  CAS  Google Scholar 

  32. Heath, C.W. Rheumatoid arthritis, aspirin, and gastrointestinal cancer. J Natl Cancer Instit 85:258–259 (editorial), 1993.

    Article  Google Scholar 

  33. Suh, O., Mettlin, C. and Petrelli, N.J. Aspirin use, cancer, and polyps of the large bowel. Cancer 72;1171–1177, 1993.

    Article  PubMed  CAS  Google Scholar 

  34. Greenberg, E.R., Baron, J.A., Freeman, D.H., Mandel, J.S. and Haile, R. Reduced risk of large-bowel adenomas among aspirin users. J Natl Cancer Instit 85:912–916, 1993.

    Article  CAS  Google Scholar 

  35. Logan R.F.A., Little J., Hawtin P.G. and Hardcastle J.D. Effect of aspirin and non-steroidal anti-inflammatory drugs on colorectal adenomasxase-control study of subjects participating in the Nottingham faecal occult blood screening programme. BMJ 307:285–289.

    Google Scholar 

  36. Gann, P.H., Manson, J.E., Glynn, J., Buring, J. and Hennekins, C.H. Low-dose aspirin and incidence of colorectal tumors a randomized trial. J Natl Cancer Instit 85:1220–1224, 1993.

    Article  CAS  Google Scholar 

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© 1997 Springer Science+Business Media New York

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Thun, M.J. (1997). Aspirin and Gastrointestinal Cancer. In: Honn, K.V., Nigam, S., Marnett, L.J. (eds) Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury 2. Advances in Experimental Medicine and Biology, vol 400. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5325-0_53

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  • DOI: https://doi.org/10.1007/978-1-4615-5325-0_53

  • Publisher Name: Springer, Boston, MA

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