Effect of Caloric Restriction on Colonie Proliferation in Obese Persons: Implications for Colon Cancer Prevention1

Dietary intervention to prevent colon cancer is a major health issue. At present it is not clear which dietary factors modify colon cancer risk. Caloric restriction reduces the incidence of many spontaneous and car cinogen-induced tumors in rodents, but its role in human carcinogenesis is unknown. The relationships of body mass index (BMI), body composition, and resting metabolic rate (RMR) to colon cancer risk are also undefined. In this study involving obese persons, we measured the effect of reducing caloric intake on rectal cell proliferation, a biomarker in colon carcino genesis, and studied the relation of BMI, body composition, and RMR to rectal cell proliferation. Colonie cell proliferation was measured in rectal biopsies from persons weighing more than 130% of ideal body weight. Follow-up biopsies were performed in patients who enrolled in and com pleted a 16-week behavior modification weight-reduction program in which caloric intake was reduced. Baseline measurements included body composition by total body electrical conductance, RMR, and BMI. Rectal biopsies were processed for autoradiography following incubation with pHjthymidine. Epithelial proliferation measurements were évaluablein 35 persons at baseline and in 8 persons before and after caloric restriction. Before caloric restriction, mean (±SD) BMI was 38 ±4 kg/m2 and per centage of body fat 41 ±2%. Subjects reduced their caloric intake by a mean of 34 ±4% and their weight by 8.6 ±1%. Caloric restriction resulted in a 39% reduction in whole-crypt labeling index (P < 0.001) and a 57% reduction in upper crypt labeling index (P < 0.05) without reduction in crypt depth. Labeling index was unrelated to BMI, RMR, or body com position. We conclude that caloric restriction reduced rectal cell prolif eration measurements—intermediate biomarkers related to colon carci nogenesis. BMI, RMR, and body composition were unrelated to colonie proliferation. Caloric restriction may have a role in colon cancer preven tion.