DIETARY-FAT INFLUENCES ON POLYP PHENOTYPE IN MULTIPLE INTESTINAL NEOPLASIA MICE

Significant differences in colon cancer incidence worldwide have led t o the hypothesis that this variation can be explained largely by envir onmental, notably dietary influences, Although a positive correlation between dietary fat intake and incidence is suggested fi om some human epidemiological and rodent carcinogenesis studies, a direct associati on remains contentious, Using a spontaneous mouse tumor model of multi ple intestinal neoplasia, we demonstrate that there is a generalized i ncrease in tumor counts, in both the large and small bowel with higher dietary fat [standard (3%) fat versus high (15%) fat diet (mean +/- S D) 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 incre ases polyp size In the small bowel, These changes appear independent o f total calorific intake as assessed by body weights, Halving the crud e 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 fa t alone to 15%, which also decreased survival (P < 0.05), These result s demonstrate that increasing dietary fat intake from weaning can have a significant adverse effect on polyp numbers In mice genetically pre disposed to intestinal tumor development, A further understanding of t he biology of this interaction may provide novel strategies aimed at b oth colonic polyp prevention and treatment.