Molecular Studies on the Role of Dietary Fat and Cholesterol in Breast Cancer Induction

  • Michael C. Archer
  • Ahmed El-Sohemy
  • Laurie L. Stephen
  • Alaa F. Badawi
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 422)


It has been known for many years that rates of breast cancer vary five to ten-fold between countries1. Furthermore, migrants from low to high-risk countries adopt the rates of their new country2. This type of evidence, albeit indirect, strongly suggests that environmental factors play a role in breast cancer development. There is also substantial evidence that genetic and hormonal factors contribute significantly.3,4 Although there are many hypotheses to account for the role of the environment, diet is undoubtedly one of the most important.5 A number of years ago, Doll and Peto estimated that as much as 50% of breast cancer in North America might be prevented by changes in diet.6


Breast Cancer Mammary Gland Dietary Cholesterol Breast Cancer Development Mammary Carcinogenesis 
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.


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  1. 1.
    International Agency for Research on Cancer. Cancer Incidences on Five Continents. IARC Sci. Publ., 5: 882–883, 1987.Google Scholar
  2. 2.
    Haenszel, W. Migrant studies. In: D. Schottenfeld and J.F. Fraumeni (Eds) Cancer Epidemiology and Prevention, W.B. Saunders, Philadelphia, PA, pp. 194–207, 1982.Google Scholar
  3. 3.
    Eby, N., Chang-Claude, J. and Bishop, D.T. Familial risk and genetic susceptibility for breast cancer. Cancer Causes Control, 5: 458–470, 1994.CrossRefGoogle Scholar
  4. 4.
    Henderson, B.E., Ross, R.K., Pike, M.C. and Casagrande, J.T. Endogenous hormones as a major factor in human cancer. Cancer Res., 42: 3232–3239, 1982.Google Scholar
  5. 5.
    Miller, A.B., Berrino, F., Hill, M., Pietinen, P., Riboli, E. and Wahrendorf, J. Diet in the aetiology of cancer: a review. Eur. J. Cancer, 30A: 207–220, 1994.CrossRefGoogle Scholar
  6. 6.
    Doll, R. and Peto, R. The causes of cancer. J. Natl. Cancer Inst., 66: 1191–1308, 1981.Google Scholar
  7. 7.
    Willet, W. The search for the causes of breast and colon cancer. Nature, 338: 389–394, 1989.CrossRefGoogle Scholar
  8. 8.
    Carroll, K.K., Braden, L.M., Bell, J.A. and Kalamegham, R. Fat and cancer. Cancer, 58: 1818–1825, 1986.CrossRefGoogle Scholar
  9. 9.
    Mendola, P., Marshall, J., Graham, S., Laughlin, R.H. and Freudenheim, J.L. Dietary correlates of fat. Nutr. Cancer, 23: 161–169, 1995CrossRefGoogle Scholar
  10. 10.
    Hunter, D.J., Spieglman, D., Adami, H-0., Beeson, L., van den Brandt, P.A., Folsom, A.R., Fraser, G.E., Goldbohm, A., Graham, S., Howe, G.R., Kushi, L.H., Marshall, J.R., McDermott, A., Miller, A.B., Speizer, F.E., Wolk, A., Yaun, S-S. and Willet, W. Cohort studies of fat intake and the risk of breast cancer-a pooled analysis. N. Engl. J. Med. 334: 356–61, 1996.Google Scholar
  11. 11.
    Willett, W.C., Hunter, D.J., Stampfer, M.J., Colditz, G., Manson, J.E., Spiegelman, D., Rosner, B., Hennekens, C.H. and Speizer, F.E. Dietary fat and fiber in relation to risk of breast cancer: an 8-year follow up. JAMA, 268: 2037–2044. 1992.CrossRefGoogle Scholar
  12. 12.
    Goodwin, P.J. and Boyd, N.F. Critical appraisal of the evidence that dietary fat intake is related to breast cancer in humans. J. Natl. Cancer Inst., 79: 473–485, 1987.Google Scholar
  13. 13.
    Bingham, S.A., Gill, C., Welch, A., Day, K., Cassidy, A., Khaw, K.T., Sneyd, M.J., Key, T.J.A., Roe, L. and Day, N.E. Comparison of dietary assessment methods in nutritional epidemiology: weighed records v. 24h recalls, food-frequency questionnaires and estimated-diet records. Br. J. Nutr., 72: 619–643, 1994.CrossRefGoogle Scholar
  14. 14.
    McMichael, A.J., Jensen, 0.M., Parkin, D.M. and Zaridze, D.G. Dietary and endogenous cholesterol and human cancer. Epidemiol. Rev., 6: 192–216, 1984.Google Scholar
  15. 15.
    Cowan, L.D., O’Connell, D.L., Criqui, M.H., Barrett-Connor, E., Bush, T.L., et al. Cancer mortality and lipid and lipoprotein levels. The Lipid Research Clinic Program mortality follow-up study. Am. J. Epidemiol., 131: 468–482, 1990.Google Scholar
  16. 16.
    Vatten, L.J. and Foss, O.P. Total serum cholesterol and triglycerides and risk of breast cancer: a prospective study of 24,329 Norwegian women. Cancer Res., 50: 2341–2346, 1990.Google Scholar
  17. 17.
    Beynen, A.C., Katan, M.B. and Van Zutphen, L.F.M. Hypo-and hyperresponders: individual differences in the response of serum cholesterol concentration to changes in the diet. Ad. Lipid Res., 22: 115–171, 1987.Google Scholar
  18. 18.
    Vitols, S., Bjorkholm, M., Gahrton, G. and Peterson, C. Hypocholesterolaemia in malignancy due to elevated low-density-lipoprotein-receptor activity in tumour cells: evidence from studies in patients with leukemia. Lancet, 2: 1150–1154, 1985.CrossRefGoogle Scholar
  19. 19.
    Rogers, A.E. and Lee, S.Y. Chemically-induced mammary gland tumors in rats: modulation by dietary fat. In: Ip, C. et al. Dietary Fat and Cancer. Alan R. Liss, New York, NY, pp. 255–269, 1988.Google Scholar
  20. 20.
    Thompson, H.J., Adlakha, H. and Singh, M. Effect of carcinogen dose and age at administration on induction of mammary carcinogenesis by 1-methyl-l-nitrosourea. Carcinogenesis, 13: 1535–1539, 1992.CrossRefGoogle Scholar
  21. 21.
    Russo, J. and Russo, I.H. Towards a physiological approach to breast cancer prevention. Cancer Epi. Bio. Prev., 3: 353–364, 1994.Google Scholar
  22. 22.
    Sukumar, S., Notario, V., Martin-Zanca, D. and Barbacid, M. Induction of mammary carcinomas in rats by nitroso-methylurea involves malignant activation of H-ras-l -locus by single point mutations. Nature, 306: 658–661, 1983.CrossRefGoogle Scholar
  23. 23.
    Waldmann, V., Suchy, B. and Rabes, H.M. Cell proliferation and prevalence of ras gene mutations in 7,12dimethylbenz(a)anthracene (DMBA)- induced rat mammary tumors. Res. Exp. Med., 193: 143–151, 1993.CrossRefGoogle Scholar
  24. 24.
    Zhang, P-L., Calaf, G. and Russo, J. Allele loss and point mutation in codons 12 and 61 of the c-Ha-ras oncogene in carcinogen-transformed human breast epithelial cells. Mol. Carcinogenesis., 9: 46–56, 1994.CrossRefGoogle Scholar
  25. 25.
    Russo, J., Gusterson, B.A., Rogers, A.E., Russo, 1.H., Wèllings, S.R. and Zwieten, M.J. Comparative study of human and rat mammary tumorigenesis. Lab. Invest., 62: 244–278, 1990.Google Scholar
  26. 26.
    Welsch, C.W. Relationship between dietary fat and experimental mammary tumorigenesis: a review and critique. Cancer Res., 52: 2040s - 2048s, 1992.Google Scholar
  27. 27.
    Lu, S-J. and Archer, M.C. Ha-ras activation in mammary glands of N-methyl-N-nitrosourea-treated rats genetically resistant to mammary adenocarcinogenesis. Proc. Natl. Acad. Sci. USA, 89: 1001–1005, 1992.CrossRefGoogle Scholar
  28. 28.
    Hu, Z., Chaulk, J.E., Lu, S-L., Xu, Z. and Archer, M.C. Effect of dietary fat or tamoxifen on the expansion of cells harboring Ha-ras oncogenes in mammary glands from methylnitrosourea-treated rats. Carcinogenesis, 16: 2281–2284, 1995.CrossRefGoogle Scholar
  29. 29.
    Cohen, L.A. and Chan, P-C. Dietary cholesterol and experimental mammary cancer development. Nutr. Cancer, 4: 99–106, 1982.CrossRefGoogle Scholar
  30. 30.
    Karmali, R.A., Welt, S., Thaler, H.T., and Lefevre F. Prostaglandins in breast cancer. Relationship to disease stage and hormone status. Br. J. Cancer., 48: 689–696, 1983.CrossRefGoogle Scholar
  31. 31.
    Tan, W.C., Privett, O.S., and Goldyne, M.E. Studies of prostaglandins in rat mammary tumors induced by 7,12-dimethylbenz(a)anthracene. Cancer Res., 34: 3229–3231, 1974.Google Scholar
  32. 32.
    O’Neill, G.P., and Ford-Hutchinson, A. Expression of mRNA for cyclooxygenase-I and cyclooxygenase-2 in human tissues. FEBS Lett., 2: 156–160, 1993.Google Scholar
  33. 33.
    Sander, B.D., Addis. P.B., Park, S.W. and Smith, E.D. Quantification of cholesterol oxidation products in a variety of foods. J. Food Protein, 52: 109–114, 1989.Google Scholar
  34. 34.
    Morin, R.J., Hu, B., Peng, S-K. and Sevanian, A. Cholesterol oxides and carcinogenesis. J. Clin. Lab. Anal., 5: 219–225, 1991.CrossRefGoogle Scholar
  35. 35.
    Petrakis, N.L., Gruenke, L.D. and Craig, J.C. Cholesterol and cholesterol epoxides in nipple aspirates of human breast fluid. Cancer Res., 41: 2563–2565, 1981.Google Scholar
  36. 36.
    EI-Sohemy, A., Bruce, W.R. and Archer, M.C. Inhibition of rat mammary tumorigenesis by dietary cholesterol. Carcinogenesis. 17: 159–162, 1996.CrossRefGoogle Scholar
  37. 37.
    El-Bayoumy, K., Ji, B-Y., Upadhyaya, P., Chae, Y-H., Kurtzke, C. Rivenson, A., Reddy, B.S.,, S. and Hecht, S.S. Lack of tumorigenicity of cholesterol epoxides and esterone-3,4-quinone in the rat mammary gland. Cancer Res., 56: 1970–1973, 1996.Google Scholar
  38. 38.
    Chan, P-C., Head, J.F., Cohen, L.A. and Wynder, E.L. Influence of dietary fat on the induction of mammary tumors by N-nitrosourea: associated hormone changes and differences between Sprague-Dawley and F344 rats. J. Natl. Cancer Inst., 59: 1279–1283, 1977.Google Scholar
  39. 39.
    Klurfeld, D.M. and Kritchevsky, D. Serum cholesterol and 7,12-dimethylbenz[a]anthracene-induced mammary carcinogenesis. Cancer Lett., 14: 273–278, 1981.CrossRefGoogle Scholar
  40. 40.
    Brown, M.S. and Goldstein, J.L. A receptor-mediated pathway for cholesterol homeostasis. Science, 232: 34–47, 1986.CrossRefGoogle Scholar
  41. 41.
    Siperstein, M.D. Cholesterol, cholesterogenesis and cancer. Adv. Exp. Med. Biol., 369: 155–166, 1995.CrossRefGoogle Scholar
  42. 42.
    Schmidt, R.A., Schneider, C.J. and Glomset, J.A. Evidence for post-translational incorporation of a product of mevalonic acid into Swiss 3T3 cell proteins. J. Biol. Chem., 259: 10175–10180, 1984.Google Scholar
  43. 43.
    Nakayama, M., Ju, H.R., Sugano, M., Hirose, N., Ueki, T., Doi, F. and Eynard, A.R. Effect of dietary fat and cholesterol on dimethylbenz[a]anthracene-induced mammary tumorigenesis in Sprague-Dawley rats. Anticancer Res., 13: 691–698, 1993.Google Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Michael C. Archer
    • 1
  • Ahmed El-Sohemy
    • 1
  • Laurie L. Stephen
    • 1
  • Alaa F. Badawi
    • 1
  1. 1.Department of Nutritional Sciences Faculty of MedicineUniversity of TorontoTorontoCanada

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