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Significant differences in colon cancer incidence worldwide have led to the hypothesis that this variation can be explained largely by environmental, notably dietary influences. Although a positive correlation between dietary fat intake and incidence is suggested from some human epidemiological and rodent carcinogenesis studies, a direct association remains contentious. Using a spontaneous mouse tumor model of multiple intestinal neoplasia, we demonstrate that there is a generalized increase in tumor counts, in both the large and small bowel with higher dietary fat [standard (3%) fat versus high (15%) fat diet (mean +/- SD) 1.59 +/- 1.46 vs. 3.85 +/- 2.37 P < 0.001 and 21.36 +/- 7.4 vs. 31.3 +/- 9.7, respectively, P < 0.001]. Increasing dietary fat also increases polyp size in the small bowel. These changes appear independent of total calorific intake as assessed by body weights. Halving the crude fiber intake together with an increase in dietary fat from 3% to 10% did not have as marked an effect on tumor counts as an increase of fat alone to 15%, which also decreased survival (P < 0.05). These results demonstrate that increasing dietary fat intake from weaning can have a significant adverse effect on polyp numbers in mice genetically predisposed to intestinal tumor development. A further understanding of the biology of this interaction may provide novel strategies aimed at both colonic polyp prevention and treatment.

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

01/04/1997

Volume

94

Pages

3308 - 3313

Keywords

Animals, Colon, Dietary Fats, Female, Intestinal Neoplasms, Intestinal Polyps, Intestine, Small, Mammary Neoplasms, Experimental, Mice, Mice, Inbred C57BL, Neoplasms, Multiple Primary, Phenotype