EFFECT OF CALORIC RESTRICTION ON COLONIC PROLIFERATION IN OBESE PERSONS - IMPLICATIONS FOR COLON-CANCER PREVENTION

Dietary intervention to prevent colon cancer is a major health issue. At present it is not clear which dietary factors modify colon cancer r isk Caloric restriction reduces the incidence of many spontaneous and carcinogen-induced tumors in rodents, but its role in human carcinogen esis is unknown. The relationships of body mass index (BMI), body comp osition, and resting metabolic rate (RMR) to colon cancer risk are als o undefined. In this study involving obese persons, we measured the ef fect of reducing caloric intake on rectal cell proliferation, a biomar ker in colon carcinogenesis, and studied the relation of BMI, body com position, and RMR to rectal cell proliferation. Colonic cell prolifera tion was measured in rectal biopsies from persons weighing more than 1 30% of ideal body weight. Follow-up biopsies were performed in patient s who enrolled in and completed a 16-week behavior modification weight -reduction program in which caloric intake was reduced, Baseline measu rements included body composition by total body electrical conductance , RMR, and BMI. Rectal biopsies were processed for autoradiography fol lowing incubation with [H-3]thymidine. Epithelial proliferation measur ements were evaluable in 35 persons at baseline and in 8 persons befor e and after caloric restriction. Before caloric restriction, mean (+/- SD) BMI was 38 +/- 4 kg/m(2) and percentage of body fat 41 +/- 2%. Su bjects reduced their caloric intake by a mean of 34 +/- 4% and their w eight by 8.6 +/- 1%. Calorie restriction resulted in a 39% reduction i n whole-crypt labelling index (P < 0.001) and a 57% reduction in upper crypt labelling index (P < 0.05) without reduction in crypt depth. La belling index was unrelated to BMI, RMR, or body composition. me concl ude that calorie restriction reduced rectal cell proliferation measure ments-intermediate biomarkers related to colon carcinogenesis. BMI, RM R, and body composition were unrelated to colonic proliferation. Calor ic restriction may have a role in colon cancer prevention.