Aberrant crypt focus promotion and glucose intolerance: correlation in the rat across diets differing in fat, n-3 fatty acids and energy

McKeown-Eyssen (Cancer Epidemiol. Biomarkers Prevent., 3, 687-695, 1994)and Giovannucci (Cancer Causes Control, 6, 164-179, 1995), noting thestriking similarity in lifestyle risk factors for colorectal cancer andinsulin resistance, proposed that the hyperinsulinemia, glycemia andhypertriglyceridemia associated with insulin resistance promotes coloncancer. To compare the effect of diet on colon cancer promotion and insulinresistance in the F344 rat, we assessed the effect of fat, n-3 fatty acidsand energy in pairwise comparisons on average size of aberrant crypt foci(ACF) and on glucose intolerance in the same animals in a singleexperiment. Diets high in fat and energy increased and diets with increasedn-3 fatty acids and calorie restriction decreased both ACF growth andglucose intolerance compared with control diets. The measures of promotionof colon cancer and insulin resistance were strongly correlated (n = 98, r= 0.67, P < 0.001). In addition, both were highly correlated with dailyenergy intake (r = 0.62 and 0.66) and were also correlated with basal(post-prandial) insulin, glucose and triglycerides (r = 0.31-0.53, P <0.01). We concluded that ACF growth and glucose intolerance are correlatedfor a wide range of diets and that increased circulating energy (glucoseand triglycerides) may lead to both colon cancer promotion and insulinresistance.