Skip to main content
Download PDF
  • Review
  • Published:

Nutrition, metabolism and colorectal cancer

Genes & Nutrition volume 3, pages 15–17 (2008)Cite this article

Abstract

Colorectal cancer and myocardial infarction are associated at population level and in autoptic studies. Furthermore, they share many blood variables: cholesterol, triglycerides and HDL cholesterol, fructosamine, glycated haemoglobin and glycated apolipoprotein B. These blood variables are intermediates between dietary, mainly saturated fats and high glycemic index and load diets, and colorectal cancer and myocardial infarction. Blood intermediate variables can be used in dietary trials as outcomes, and even to throw light on the pathogenesis of both diseases.

Introduction

Mortality for colorectal cancer (CRC) and for myocardial infarction (MI) are associated at population level [39]. Correa et al. [7] found in an autopsy study on 842 autopsies, that the most extensive atherosclerotic involvement of the aorta was in subjects with adenomatous polyps of the colon, and even more in subjects with adenonomatous and hyperplastic polyps together. Furthermore, Stemmerman [35] in an autopsy study on 288 autopsies found that the degree of the atherosclerosis of the coronary arteries and aorta was positively and significantly related not only to the presence of adenomatous polyps, but also to their size, multiplicity and degree of atypia as well.

MI and CRC can share a common cause, a common intermediate factor or both. In this review we explore the possibility that MI and CRC not only share some common cause, but also some common intermediate factors.

Metabolism, myocardial infarction and colorectal cancer

It is known that MI is associated with high blood cholesterol, LDL cholesterol and triglycerides and low HDL cholesterol [22], however these associations are weaker and even uncertain in old people [29]. Furthermore, MI is associated with the metabolic syndrome and with diabetes [15].

In non-diabetic subjects, MI is associated with HbA1c [16], as well as with fructosamine, an index of glycated proteins in the blood, at least in women [4], and with glycated apolipoprotein B [28].

Several studies have evaluated the association between serum cholesterol and colorectal adenomatous polyps or carcinoma in situ [1, 2, 8, 13, 19, 20, 24, 40]. Most but not all of these studies found an association of colorectal adenoma or cancer in situ with serum cholesterol. Serum triglycerides were associated with colorectal adenoma [25, 32], and with colorectal cancer in situ [40]. CRC was found associated with the metabolic syndrome [6, 37]. CRC and adenomas are associated with diabetes or prediabetes [14, 17, 18, 21, 23, 30, 33, 38, 41]. We found that fructosamine is associated with colorectal adenoma [27], as well as glycated apolipoprotein B with colorectal adenoma and cancer (Misciagna et al., unpublished data).

Diet, myocardial infarction and colorectal cancer

The association of both MI and CRC with blood lipids and non enzymatic glycated serum proteins also in non diabetic subjects allows to study the effects of diet on MI and CRC through the effects of diet on these intermediate variables. Cholesterol, triglycerides and HDL cholesterol are influenced by both saturated fats and sugars in the diet [5, 9], glycated haemoglobin is influenced by saturated fats in the diet [3, 11, 12], fructosamine by glycemic index and load [26], as well as glycated apolipoprotein B (Misciagna et al., unpublished data). All these results show that MI and CRC are associated with a diet rich in saturated fats and at high glycemic index and load.

Conclusions

The results of many epidemiological studies show that MI and CRC share many intermediate variables: cholesterol, cholesterol HDL, triglycerides, glycated haemoglobin and apoliprotein B, fructosamine. Furthermore, using the relationship of diet with these intermediate blood variables, it is possible to deduce that dietary saturated fats, glycemic index and load are associated with CRC and MI. The discovery of blood intermediate variables between diet and MI and CRC can open the way to trials of the effects of diet on these variables, to add evidence to the results of the observational epidemiological studies on diet and cardiovascular diseases or colorectal cancer.

Myocardial infarction and colorectal cancer share some dietary causes and intermediate variables, do they share also some pathogenetic mechanisms ?

Glycated ApoB has been found in the macrophages of the arterial wall, in the fatty streaks of atherosclerotic vessels [36]. In fact, macrophages prefer glycated, oxidized or glyco-oxidized lipoproteins for their scavenger receptors, not the normal ones [34].

It is known that neoplastic cells behave like a macrophage and have a strong phagocytic activity [10, 31], so may be colorectal cancer too, like the macrophages of the arterial wall in atherosclerosis, “eats” glycated lipoprotein.

References

  1. Bayerdorffer E, Mannes GA, Richter WO, et al (1993) Decreased high-density lipoprotein cholesterol and increased low-density cholesterol levels in patients with colorectal adenomas. Ann Int Med 118:481–487

    PubMed  CAS  Google Scholar 

  2. Bird CL, Ingles SA, Frankl HD, Lee ER, Longnecker MP, Haile RW (1996) Serum lipids and adenoma of the left colon and rectum. Cancer Epidemiol Biomark Prev 5:607–612

    CAS  Google Scholar 

  3. Boeing H, Weisgerber UM, Jeckel A, Rose HJ, Kroke A (2000) Association between glycated hemoglobin and diet and other lifestyle factors in a non diabetic population: cross-sectional evaluation of data from the Potsdam cohort of the EPIC Study. Am J Clin Nutr 71:1115–1122

    PubMed  CAS  Google Scholar 

  4. Browner WS, Pressman AR, Lui LY, Cummings SR (1999) Association between serum fructosamine and mortality in elderly women: the study of osteoporotic fractures. Am J Epidemiol 149:471–475

    PubMed  CAS  Google Scholar 

  5. Chong MF, Fielding BA, Frayn KN (2007) Metabolic interaction of dietary sugars and plasma lipids with a focus on mechanisms and de novo lipogenesis. Proc Nutr Soc 66:52–59

    Article  PubMed  CAS  Google Scholar 

  6. Colangelo LA, Gapstur SM, Gann PH, Dyer AR, Liu K (2002) Colorectal cancer mortality and factors related to the insulin resistance syndrome. Cancer Epidemiol Biomark Prev 11:385–391

    Google Scholar 

  7. Correa P, Strong JP, Johnson WD, Pizzolato P, Haenszel W (1982) Atherosclerosis and polyps of the colon. Quantification of precursors of coronary heart disease and colon cancer. J Chronic Dis 35:313–320

    Article  PubMed  CAS  Google Scholar 

  8. Demers RY, Neale AV, Demers P, et al (1988) Serum cholesterol and colorectal polyps. J Clin Epidemiol 41:9–13

    Article  PubMed  CAS  Google Scholar 

  9. Denke MA (2006) Dietary fats, fatty acids, and their effects on lipoproteins. Curr Atheroscler Rep 8:466–471

    Article  PubMed  CAS  Google Scholar 

  10. Fais S (2007) Cannibalism: a way to feed on metastatic tumors. Cancer Lett 258:155–164

    Article  PubMed  CAS  Google Scholar 

  11. Gulliford MC, Ukoumunne OC (2001) Determinants of glycated haemoglobin in the general population: association with diet, alcohol and cigarette smoking. Eur J Clin Nutr 55:615–623

    Article  PubMed  CAS  Google Scholar 

  12. Harding AH, Sargeant LA, Welch A, et al (2001) Fat consumption and HbA1c levels. Diabetes Care 24:1911–1916

    Article  PubMed  CAS  Google Scholar 

  13. Houghton J, Lardieri GG, Zauber P, Kim KH, Cable G (2000) Effect of cholesterol levels on villous histology in colonic adenomas. Dig Dis Sci 45:896–899

    Article  PubMed  CAS  Google Scholar 

  14. Hu FB, Manson JE, Liu S, et al (1999) Prospective study of adult onset diabetes mellitus (type 2) and risk of colorectal cancer in women. J Natl Cancer Inst 91:542–547

    Article  PubMed  CAS  Google Scholar 

  15. Hu G, Qiao Q, Tuomilehto J (2005) Metabolic syndrome, diabetes, and coronary heart disease. In: Qiao Q, Tuomiletho J, Marmot M, Elliott P (eds) Coronary heart disease epidemiology. 2nd edn. Oxford University Press, New York pp 311–330

    Google Scholar 

  16. Khaw KT, Wareham N, Bingham S, Luben R, Welch A, Day N (2004) Association of hemoglobin A1c with cardiovascular disease and mortality in adults: the European prospective investigation into cancer in Norfolk. Ann Intern Med 141:413–420

    PubMed  CAS  Google Scholar 

  17. Khaw KT, Wareham N, Bingham S, Luben R, Welch A, Day N (2004) Preliminary communication: glycated hemoglobin, diabetes, and incident colorectal cancer in men and women: a prospective analysis from the European prospective investigation into cancer-Norfolk study. Cancer Epidemiol Biomarkers Prev 13:915–919

    PubMed  Google Scholar 

  18. Kono S, Honjo S, Todoroki I, et al (1998) Glucose intolerance and adenomas of sigmoid colon in Japanese men. Cancer Causes Control 9:441–446

    Article  PubMed  CAS  Google Scholar 

  19. Kono S, Imanishi K, Shinchi K, Yanai F (1993) Serum lipids and left-sided adenomas of the large bowel: An extended study of self-defense official in Japan. Cancer Causes Control 4:117–121

    Article  PubMed  CAS  Google Scholar 

  20. Kono S, Ikeda N, Yanai F, Yamamoto M, Shigematsu T (1990) Serum lipids and colorectal adenoma among male self defence officials in northern Kyushu, Japan. Int J Epidemiol 19:274–278

    Article  PubMed  CAS  Google Scholar 

  21. La Vecchia C, Negri E, Decarli A, Franceschi S (1997) Diabetes mellitus and colorectal cancer risk. Cancer Epidemiol Biomark Prev 6:1007–1010

    CAS  Google Scholar 

  22. Law MR, Rodgers A (2005) Lipids and cholesterol. In: Marmot M, Elliott P (eds) Coronary heart disease epidemiology. 2nd edn. Oxford University Press, New York, pp 174–186

    Google Scholar 

  23. Levine W, Dyer AR, Shekelle RB, Schoenberger JA, Stamler J (1990) Post-load plasma glucose and cancer mortality in middle-aged men and women. 12-year follow up findings of the Chicago heart association detection project in industry. Am J Epidemiol 131:254–262

    PubMed  CAS  Google Scholar 

  24. Mannes GA, Maier A, Thieme C, Wiebecke B, Paumgartner G (1986) Relation between the frequency of colorectal adenoma and the serum cholesterol level. N Engl J Med 315:1634–1638

    Article  PubMed  CAS  Google Scholar 

  25. McKeown-Eyssen GE, and the Toronto Polyp Prevention Group (1996) Insulin resistance and the risk of colorectal neoplasia. Cancer Epidemiol Biomark Prev 5:235–247

    Google Scholar 

  26. Misciagna G, De Michele G, Cisternino AM, Guerra V, Logroscino G, Freudenheim JL (2005) Dietary carbohydrates and glycated proteins in the blood in non diabetic subjects. J Am Coll Nutr 24:22–29

    PubMed  CAS  Google Scholar 

  27. Misciagna G, De Michele G, Guerra V, Cisternino AM, Di Leo A, Freudenheim JL, INTEROSP Group (2004) Serum fructosamine and colorectal adenomas. Eur J Epidemiol 19:425–432

    Article  PubMed  CAS  Google Scholar 

  28. Misciagna G, Logroscino G, De Michele G, Guerra V, Cisternino AM, Caruso MG, Trevisan M (2007) Glycated apolipoprotein B and myocardial infarction. Nutr Metab Cardiovasc Dis 17:6–12

    Article  PubMed  CAS  Google Scholar 

  29. Ravnskov U (2000) The cholesterol myths. New Trends Publishing, Washington DC, pp 47–95

    Google Scholar 

  30. Sandhu MS, Luben R, Khaw KT (2001) Self reported noninsulin dependent diabetes, family history, and risk of 431 prevalent colorectal cancer: population based, cross sectional study. Gut 42:804–805

    Google Scholar 

  31. Sato K, Tsuchihara K, Fujii S, Sugiyama M, Goya T, Atomi Y, Ueno T, Ochiai A, Esumi H (2007) Autophagy is activated in colorectal cancer cells and contributes to the tolerance to nutrient deprivation. Cancer Research 67:9677–9684

    Article  PubMed  CAS  Google Scholar 

  32. SchoenBird CL, Ingles SA, Frankl HD, Lee ER, Longnecker MP, Haile RW (1996) Serum lipids and adenoma of the left colon and rectum. Cancer Epidemiol BiomarkPrev 5:607–612

    Google Scholar 

  33. Smith GD, Egger M, Shipley MJ, Marmot MG (1992) Postchallenge glucose concentration, impaired glucose tolerance, diabetes, and cancer mortality in men. Am J Epidemiol 136:1110–1114

    PubMed  CAS  Google Scholar 

  34. Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL (1989) Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 320:915–924

    Article  PubMed  CAS  Google Scholar 

  35. Stemmerman GN, Heilbrun LK, Nomura AMY, Yano K, Hayashi T (1986) Adenomatous polyps and atherosclerosis: an autopsy study of Japanese men in Hawaii. Int J Cancer 38:789–794

    Article  Google Scholar 

  36. Stitt AW, He C, Friedman S, Scher L, Rossi P, Ong L, et al (1997) Elevated AGE-modified ApoB in sera of euglycemic, normolipidemic patients with atherosclerosis: relationship to tissue AGEs. Mol Med 3:617–627

    PubMed  CAS  Google Scholar 

  37. Trevisan M, Liu J, Muti P, Misciagna G, Menotti A, Fucci F, RIFLE Group (2001) Markers of insulin resistance and colorectal cancer mortality. Cancer Epidemiol Biomark Prev 10:937–941

    Google Scholar 

  38. Will JC, Galuska DA, Vinicor F, Calle EE (1998) Colorectal cancer: another complication of diabetes mellitus? Am J Epidemiol 147:816–825

    PubMed  CAS  Google Scholar 

  39. Wynder EL, Shigematsu T (1967) Environmental factors of cancer of the colon and rectum. Cancer 20:1520–1561

    Article  PubMed  CAS  Google Scholar 

  40. Yamada K, Araki S, Tamura M, et al (1998) Relation of serum total cholesterol, serum triglycerides and fasting plasma glucose to colorectal carcinoma in situ. Int J Epidemiol 27:794–798

    Article  PubMed  CAS  Google Scholar 

  41. Zeliniuch-Jacquotte A, Shore RE, Riboli E (2000) Serum C peptide, insulin-like growth factor (IGF)-I, IGF-binding proteins, and colorectal cancer risk in women. J Natl Cancer Inst 92:1592–1600

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Epidemiology, IRCCS De Bellis, Castellana Grotte, Bari, 70013, Italy

    G. Misciagna

  2. Laboratory of Biochemistry, IRCCS De Bellis, Castellana Grotte, Bari, 70013, Italy

    M. G. Caruso

  3. University of Nevada, Health Sciences System, Las Vegas, NV, USA

    M. Trevisan

Authors
  1. G. Misciagna
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. G. Caruso
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Trevisan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G. Misciagna.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Misciagna, G., Caruso, M.G. & Trevisan, M. Nutrition, metabolism and colorectal cancer. Genes Nutr 3, 15–17 (2008). https://doi.org/10.1007/s12263-008-0080-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12263-008-0080-7

Keywords

Genes & Nutrition

ISSN: 1865-3499

Contact us