Skip to main content
Gut logoLink to Gut
. 1996 Feb;38(2):254–259. doi: 10.1136/gut.38.2.254

Changes of the mucosal n3 and n6 fatty acid status occur early in the colorectal adenoma-carcinoma sequence.

F Fernández-Bañares 1, M Esteve 1, E Navarro 1, E Cabré 1, J Boix 1, A Abad-Lacruz 1, J Klaassen 1, R Planas 1, P Humbert 1, C Pastor 1, M A Gassull 1
PMCID: PMC1383033  PMID: 8801207

Abstract

Despite data favouring a role of dietary fat in colonic carcinogenesis, no study has focused on tissue n3 and n6 fatty acid (FA) status in human colon adenoma-carcinoma sequence. Thus, FA profile was measured in plasma phospholipids of patients with colorectal cancer (n = 22), sporadic adenoma (n = 27), and normal colon (n = 12) (control group). Additionally, mucosal FAs were assessed in both diseased and normal mucosa of cancer (n = 15) and adenoma (n = 21) patients, and from normal mucosa of controls (n = 8). There were no differences in FA profile of both plasma phospholipids and normal mucosa, between adenoma and control patients. There were considerable differences, however, in FAs between diseased and paired normal mucosa of adenoma patients, with increases of linoleic (p = 0.02), dihomogammalinolenic (p = 0.014), and eicosapentaenoic (p = 0.012) acids, and decreases of alpha linolenic (p = 0.001) and arachidonic (p = 0.02) acids in diseased mucosa. A stepwise reduction of eicosapentaenoic acid concentrations in diseased mucosa from benign adenoma to the most advanced colon cancer was seen (p = 0.009). Cancer patients showed lower alpha linolenate (p = 0.002) and higher dihomogammalinolenate (p = 0.003) in diseased than in paired normal mucosa. In conclusion changes in tissue n3 and n6 FA status might participate in the early phases of the human colorectal carcinogenesis.

Full text

PDF
254

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anti M., Armelao F., Marra G., Percesepe A., Bartoli G. M., Palozza P., Parrella P., Canetta C., Gentiloni N., De Vitis I. Effects of different doses of fish oil on rectal cell proliferation in patients with sporadic colonic adenomas. Gastroenterology. 1994 Dec;107(6):1709–1718. doi: 10.1016/0016-5085(94)90811-7. [DOI] [PubMed] [Google Scholar]
  2. Anti M., Marra G., Armelao F., Bartoli G. M., Ficarelli R., Percesepe A., De Vitis I., Maria G., Sofo L., Rapaccini G. L. Effect of omega-3 fatty acids on rectal mucosal cell proliferation in subjects at risk for colon cancer. Gastroenterology. 1992 Sep;103(3):883–891. doi: 10.1016/0016-5085(92)90021-p. [DOI] [PubMed] [Google Scholar]
  3. Awad A. B., Fink C. S., Horvath P. J. Alteration of membrane fatty acid composition and inositol phosphate metabolism in HT-29 human colon cancer cells. Nutr Cancer. 1993;19(2):181–190. doi: 10.1080/01635589309514248. [DOI] [PubMed] [Google Scholar]
  4. Bartram H. P., Gostner A., Scheppach W., Reddy B. S., Rao C. V., Dusel G., Richter F., Richter A., Kasper H. Effects of fish oil on rectal cell proliferation, mucosal fatty acids, and prostaglandin E2 release in healthy subjects. Gastroenterology. 1993 Nov;105(5):1317–1322. doi: 10.1016/0016-5085(93)90135-y. [DOI] [PubMed] [Google Scholar]
  5. Bennett A., Civier A., Hensby C. N., Melhuish P. B., Stamford I. F. Measurement of arachidonate and its metabolites extracted from human normal and malignant gastrointestinal tissues. Gut. 1987 Mar;28(3):315–318. doi: 10.1136/gut.28.3.315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Blot W. J., Lanier A., Fraumeni J. F., Jr, Bender T. R. Cancer mortality among Alaskan natives, 1960-69. J Natl Cancer Inst. 1975 Sep;55(3):547–554. doi: 10.1093/jnci/55.3.547. [DOI] [PubMed] [Google Scholar]
  7. Brynskov J., Tvede N., Andersen C. B., Vilien M. Increased concentrations of interleukin 1 beta, interleukin-2, and soluble interleukin-2 receptors in endoscopical mucosal biopsy specimens with active inflammatory bowel disease. Gut. 1992 Jan;33(1):55–58. doi: 10.1136/gut.33.1.55. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Burnstein M. J. Dietary factors related to colorectal neoplasms. Surg Clin North Am. 1993 Feb;73(1):13–29. doi: 10.1016/s0039-6109(16)45926-8. [DOI] [PubMed] [Google Scholar]
  9. Butcher R. D., Wojcik S. J., Lints T., Wilson T., Schofield P. C., Ralph R. Arachidonic acid, a growth signal in murine P815 mastocytoma cells. Cancer Res. 1993 Jul 15;53(14):3405–3410. [PubMed] [Google Scholar]
  10. Cabré E., Periago J. L., Mingorance M. D., Fernández-Bañares F., Abad A., Esteve M., Gil A., Lachica M., González-Huix F., Gassull M. A. Factors related to the plasma fatty acid profile in healthy subjects, with special reference to antioxidant micronutrient status: a multivariate analysis. Am J Clin Nutr. 1992 Apr;55(4):831–837. doi: 10.1093/ajcn/55.4.831. [DOI] [PubMed] [Google Scholar]
  11. Craven P. A., DeRubertis F. R. Role of activation of protein kinase C in the stimulation of colonic epithelial proliferation by unsaturated fatty acids. Gastroenterology. 1988 Sep;95(3):676–685. doi: 10.1016/s0016-5085(88)80014-3. [DOI] [PubMed] [Google Scholar]
  12. Deschner E. E., Lytle J. S., Wong G., Ruperto J. F., Newmark H. L. The effect of dietary omega-3 fatty acids (fish oil) on azoxymethanol-induced focal areas of dysplasia and colon tumor incidence. Cancer. 1990 Dec 1;66(11):2350–2356. doi: 10.1002/1097-0142(19901201)66:11<2350::aid-cncr2820661117>3.0.co;2-6. [DOI] [PubMed] [Google Scholar]
  13. Eberhart C. E., Coffey R. J., Radhika A., Giardiello F. M., Ferrenbach S., DuBois R. N. Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology. 1994 Oct;107(4):1183–1188. doi: 10.1016/0016-5085(94)90246-1. [DOI] [PubMed] [Google Scholar]
  14. Fearon E. R., Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990 Jun 1;61(5):759–767. doi: 10.1016/0092-8674(90)90186-i. [DOI] [PubMed] [Google Scholar]
  15. Galli C., White H. B., Jr, Paoletti R. Brain lipid modifications induced by essential fatty acid deficiency in growing male and female rats. J Neurochem. 1970 Mar;17(3):347–355. doi: 10.1111/j.1471-4159.1970.tb02221.x. [DOI] [PubMed] [Google Scholar]
  16. Gassull M. A., Cabré E., Vilar L., Alastrue A., Montserrat A. Protein-energy malnutrition: an integral approach and a simple new classification. Hum Nutr Clin Nutr. 1984 Nov;38(6):419–431. [PubMed] [Google Scholar]
  17. Lepage G., Roy C. C. Direct transesterification of all classes of lipids in a one-step reaction. J Lipid Res. 1986 Jan;27(1):114–120. [PubMed] [Google Scholar]
  18. Minoura T., Takata T., Sakaguchi M., Takada H., Yamamura M., Hioki K., Yamamoto M. Effect of dietary eicosapentaenoic acid on azoxymethane-induced colon carcinogenesis in rats. Cancer Res. 1988 Sep 1;48(17):4790–4794. [PubMed] [Google Scholar]
  19. Neoptolemos J. P., Husband D., Imray C., Rowley S., Lawson N. Arachidonic acid and docosahexaenoic acid are increased in human colorectal cancer. Gut. 1991 Mar;32(3):278–281. doi: 10.1136/gut.32.3.278. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nishizuka Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature. 1984 Apr 19;308(5961):693–698. doi: 10.1038/308693a0. [DOI] [PubMed] [Google Scholar]
  21. Pugh S., Thomas G. A. Patients with adenomatous polyps and carcinomas have increased colonic mucosal prostaglandin E2. Gut. 1994 May;35(5):675–678. doi: 10.1136/gut.35.5.675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Reddy B. S., Maeura Y. Tumor promotion by dietary fat in azoxymethane-induced colon carcinogenesis in female F344 rats: influence of amount and source of dietary fat. J Natl Cancer Inst. 1984 Mar;72(3):745–750. [PubMed] [Google Scholar]
  23. Reddy B. S., Maruyama H. Effect of dietary fish oil on azoxymethane-induced colon carcinogenesis in male F344 rats. Cancer Res. 1986 Jul;46(7):3367–3370. [PubMed] [Google Scholar]
  24. Reddy B. S., Sugie S. Effect of different levels of omega-3 and omega-6 fatty acids on azoxymethane-induced colon carcinogenesis in F344 rats. Cancer Res. 1988 Dec 1;48(23):6642–6647. [PubMed] [Google Scholar]
  25. Sakaguchi M., Hiramatsu Y., Takada H., Yamamura M., Hioki K., Saito K., Yamamoto M. Effect of dietary unsaturated and saturated fats on azoxymethane-induced colon carcinogenesis in rats. Cancer Res. 1984 Apr;44(4):1472–1477. [PubMed] [Google Scholar]
  26. Sauter G., Nerlich A., Spengler U., Kopp R., Pfeiffer A. Low diacylglycerol values in colonic adenomas and colorectal cancer. Gut. 1990 Sep;31(9):1041–1045. doi: 10.1136/gut.31.9.1041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Telang N. T., Basu A., Kurihara H., Osborne M. P., Modak M. J. Modulation in the expression of murine mammary tumor virus, ras proto-oncogene, and of alveolar hyperplasia by fatty acids in mouse mammary explant cultures. Anticancer Res. 1988 Sep-Oct;8(5A):971–976. [PubMed] [Google Scholar]
  28. Tsai M. H., Yu C. L., Wei F. S., Stacey D. W. The effect of GTPase activating protein upon ras is inhibited by mitogenically responsive lipids. Science. 1989 Jan 27;243(4890):522–526. doi: 10.1126/science.2536192. [DOI] [PubMed] [Google Scholar]
  29. Vuilleumier J. P., Keller H. E., Gysel D., Hunziker F. Clinical chemical methods for the routine assessment of the vitamin status in human populations. Part I: The fat-soluble vitamins A and E, and beta-carotene. Int J Vitam Nutr Res. 1983;53(3):265–272. [PubMed] [Google Scholar]
  30. Willett W. C., Stampfer M. J., Colditz G. A., Rosner B. A., Speizer F. E. Relation of meat, fat, and fiber intake to the risk of colon cancer in a prospective study among women. N Engl J Med. 1990 Dec 13;323(24):1664–1672. doi: 10.1056/NEJM199012133232404. [DOI] [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES