Mechanisms of Specific Nutrients in the Prevention of Cancer

  • Michael J. Hill
Part of the Experimental Biology and Medicine book series (EBAM, volume 23)


Many dietary intervention protocols for cancer prevention have been proposed, often with little justification. However, in recent years our understanding of the mechanisms of carcinogenesis, particularly in the gastrointestinal tract, has increased enormously and we are now in a position to propose dietary interventions with a solidly rational basis, and to devise rational procedures for their rapid evaluation. In this presentation I will discuss the mechanism of action of three specific nutrients in the prevention of cancer of the gastrointestinal tract, namely ascorbic acid in the primary prevention of gastric cancer and calcium supplements or caecal acidification in the primary prevention of colorectal cancer. In both cancers it will first be necessary to review the state of our current knowledge of the mechanism of carcinogenesis, in order to be able to put the role of the specific nutrient into context.


Gastric Cancer Bile Acid Deoxycholic Acid Gastric Carcinogenesis Gastric Atrophy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Bavin M, Darkin DW, Viney NJ. Total N-nitroso groups in gastric juice. IARC Scientific Publication No 41, Lyon, 337–344 (1982).Google Scholar
  2. 2.
    Bjelke E. Epidemiological studies of cancer of the stomach, colon and rectum. Scand. J. Gastro. 9: Supplement 31 (1984).Google Scholar
  3. 3.
    Bown RL, Gibson JA, Sladen GE, Hicks B, Dawson AM. Effects of lactulose and other laxatives on ideal and colonic pH as measured by a radiotelemetry device. Gut 15: 999–1004 (1974).CrossRefGoogle Scholar
  4. 4.
    Burt RW, Bishop T, Cannon LA, Dowdle DA. Lee RG, Skolnich LH. Dominant inheritance of adenomatous colonic polyps and colorectal cancer. New Eng. J. Med. 312: 1540–1544 (1985).CrossRefGoogle Scholar
  5. 5.
    Calmels S, Ohshima H. Vincent P et al. Screening microorganisms for nitrosation catalysis at pH7 and kinetic studies on nitrosamine formation from secondary amines by E.coli strains. Carcinogenesis 6: 911–915 (1985).CrossRefGoogle Scholar
  6. 6.
    Cardesa A. Mirvish SS, Haven GT, Shubik P. Inhibitory effect of ascorbic acid on the acute toxicity of dimethylamine plus nitrite in the rat. Proc. Soc. Exp. Biol. Med. 145: 124–128 (1974).Google Scholar
  7. 7.
    Correa P. Haenszel W, Cuello C, Tannenbaum S. Archer M. A model of gastric cancer epidemiology. Lancet ii 58–60(1975).CrossRefGoogle Scholar
  8. 8.
    Fadden K, Owen R, Hill MJ et al. Steroid degradation along gastrointestinal tract: the use of the cannulated pig as a model system. Trans. Biochem. Soc. 12: 1105–6 (1984).Google Scholar
  9. 9.
    Felix YF. Thesis for Fellowship of the Institute of Med. Lab. Sciences (London ) 1987.Google Scholar
  10. 10.
    Garland C, Shekelle RB, Barrett-Conner E, Criqui MH, Rossof AH, Paul D. Dietary vitamin D and calcium and risk of colorectal cancer. Lancet i 307–309 (1985).CrossRefGoogle Scholar
  11. 11.
    Hill MJ. Steroid nuclear dehydrogenation and colon cancer. Amer. J. Clin. Nutr. 27: 1475–1480 (1974).Google Scholar
  12. 12.
    Hill MJ. Mechanisms of colorectal carcinogenesis. In (eds J. Joossens, J Geboers, MJ Hill) Diet and Human Carcinogenesis Excerpta Medica, Amsterdam. 149–164 (1985).Google Scholar
  13. 13.
    Hill MJ. Microbes and Human Carcinogenesis, Edward Arnold, London (1986).Google Scholar
  14. 14.
    Hill MJ. Gastric carcinogenesis: luminal factors. In (eds PI Reed, MJ Hill) Gastric Carcinogenesis Excerpta Medica. Amsterdam. 187–200 (1988).Google Scholar
  15. 15.
    Hill MJ. N-nitroso compounds and lung cancer. In (ed MJ Hill) N-nitroso Compounds: toxicology and bacteriology Ellis Horwood, Chichester. 142–162 (1989)Google Scholar
  16. 16.
    Hill MJ, Morson BC. Bussey HJR. Aetiology of adenomacarcinoma sequence. Lancet i: 245–247 (1978).CrossRefGoogle Scholar
  17. 17.
    Hill MJ, Morson BC, Thompson MH. The role of faecal bile acids in large bowel carcinogenesis. Br. J. Cancer 48: 143 (1983).Google Scholar
  18. 18.
    H11 MJ. Melville D, Lennard-Jones J. Neale K, Ritchie JK. Faecal bile acids dysplasia and carcinoma in ulcerative colitis. Lancet ii: 183–186 (1987).Google Scholar
  19. 19.
    Judd P. Dietary factors in the aetiology of gastric cancer. In (eds PI Reed, MJ Hill) Gastric Carcinogenesis. Excerpta Medica, Amsterdam. 87–98 (1988).Google Scholar
  20. 20.
    Lauren P. The two histological main types in gastric carcinoma: diffuse and so-called intestinal type. Acta Path. Mic. Scand 64: 31–49 (1965).Google Scholar
  21. 21.
    Leach S. Challis B, Cook AR. Hill MJ, Thompson MH. Bacterial catalysis of the N-nitrosation of secondary amines. Trans. Biochem. Soc. 13: 380–381 (1985).Google Scholar
  22. 22.
    Leach S. Mechanisms of endogenous N-nitrosation. In (ed MJ Hill) Nitrosamines: Toxicology and Microbiology Ellis Horwood, Chichester. 69–87 (1987).Google Scholar
  23. 23.
    Lipkin M. Newmark H. Effect of added dietary calcium on colonic epithelial cell proliferation in subjects at high risk for familial colonic cancer. N. Eng. J. Med. 313: 1381–1384 (1985).CrossRefGoogle Scholar
  24. 24.
    Mackerness C, Leach S, Thompson MH, Hill MJ. The inhibition of bacterially mediated N-nitrosation by vitamin C: Relevance of the inhibition of endogenous nitrosation in the achlorhydric stomach. Carcingenesis 10: 397–399 (1989).CrossRefGoogle Scholar
  25. 25.
    Midvedt T, Norman A. Breakdown of bile salts by intestinal bacteria. Acta Path. Mic. Scand. 71: 629–638 (1967).CrossRefGoogle Scholar
  26. 26.
    Milton-Thompson G, Lightfoot N. Ahmet Z. Intragastric acidity, bacteria, nitrite and N-nitroso compounds before, during and after cimetidine treatment. Lancet i: 1091–1094 (1982).CrossRefGoogle Scholar
  27. 27.
    Mirvish SS. Effects of vitamins C and E on N-nitroso compound formation. carcinogenesis and cancer. Cancer 58: 1842–1850 (1986).Google Scholar
  28. 28.
    Mirvish SS, Wallcave L. Eagen M, Shubik P. Ascorbate-nitrite reaction: possible means of blocking the formation of carcinogenic N-nitroso compounds. Science 177: 65–68 (1972).CrossRefGoogle Scholar
  29. 29.
    Mirvish SS, Cardesa A. Wallcave L. Shubik P. Induction of mouse lung adenomas by amines or ureas plus nitrite and by N-nitroso compounds: effect of ascorbate, gallic acid, thiocyanate and caffeine. J. Nat. Cancer Nut. 55: 633–636 (1975).Google Scholar
  30. 30.
    Morson BC. Factors influencing the prognosis of early cancer of the rectum. Proc. Roy. Soc. Med. 59: 607–608 (1966).Google Scholar
  31. 31.
    Morson BC. The polyp-cancer sequence of the large bowel. Proc. Roy. soc. Med. 67: 451–457 (1974).Google Scholar
  32. 32.
    Morson BC, Konishi F. Dysplasia of the colon and rectum. In (ed R Wright) Recent Advances in Gastrointestinal Pathology. R Saunders, London. 331–343 (1980).Google Scholar
  33. 33.
    Morson BC, Bussey HJR. Day D, Hill MJ. Adenomas of the large bowel. Cancer Surveys 2: 457–477 (1983).Google Scholar
  34. 34.
    Newmark H, Wargovich MJ, Bruce WR. Colon cancer and dietary fat, phosphate and calcium: A hypothesis. J. Nat Cancer Inst. 74: 1323–1325 (1984).Google Scholar
  35. 35.
    Owen RW, Thompson MH, Hill MJ, Wilpart M. Mainguet P, Roberfroid M. The importance of the ratio of lithocholic to deoxycholic acid in large bowel carcinogenesis. Nutr. Cancer 9: 67–71 (1987).CrossRefGoogle Scholar
  36. 36.
    Pignatelli B, Richard I, Bourgade M. Bartsch H. An improved method for analysis of total N-nitroso compounds in gastric juice. Analyst 112: 945–949 (1987).CrossRefGoogle Scholar
  37. 37.
    Rafter J, Eng WS, Furrer R, Medline A, Bruce WR. Effects of calcium and pH on the mucosal damage produced by deoxycholic acid in the rat colon. Gut 27: 1320–1329 (1986).CrossRefGoogle Scholar
  38. 38.
    Reed PI, Smith PL, Hines K. Gastric juice N-nitrosamines in health and gastroduodenal disease. Lancet ii: 550–552 (1981).CrossRefGoogle Scholar
  39. 39.
    Reed PI, Summers K, Smith P. Walters CL, Bartholomew B, Hill MJ. Vennitt S, Hornig D, Boneour, J-P. Effect of ascorbic acid treatment on gastric juice nitrite and N-nitroso compounds concentrations in achlorhydric subjects. Gut 24: 492–493 (1983).Google Scholar
  40. 40.
    Sharma BK. Santana IA, Wood EC, Walt R, Pereira M, Noone P. Pounder R. Smith P, Walters CL. Intragastric bacterial activity and nitrosation before, during and after treatment with omeprazole. Brit. Med. J. 289: 717–719 (1984).CrossRefGoogle Scholar
  41. 41.
    Thomas JM, Misiewicz J, Cook A. Hill MJ, Smith P. Walters CL, Forster J, Martin L, Woodings D. Effects of one years treatment with ranitidine and of truncal vagotomy on gastric contents. Gut 28: 726–738 (1987).CrossRefGoogle Scholar
  42. 42.
    Thornton JR. High colonic pH promoter colorectal cancer. Lancet i: 1081–1083 (1981).CrossRefGoogle Scholar
  43. 43.
    Walters CL, Hart RJ, Keefer L. Newberne P. The sequential determination of nitrite. N-nitroso compounds and nitrate and its application. IARC Scientific Publication No 31 Lyon 389–393 (1980).Google Scholar
  44. 44.
    Wargovich MJ, Eng V, Newmark HL, Bruce WR. Calcium ameliorates the toxic effect of deoxychoic acid on colonic epithelium. Carcinogenesis 4: 1205–1207 (1983).CrossRefGoogle Scholar

Copyright information

© The Humana Press Inc. 1990

Authors and Affiliations

  • Michael J. Hill
    • 1
  1. 1.PHLS-CAMRSalisbury, WiltshireUK

Personalised recommendations