Dietary fat, body weight, and cancer: contributions of studies in rodents to understanding these cancer risk factors in humans

Understanding diet and energy balance as risk factors for breast, colon,and other cancers requires information on the contribution of each factorand of interactions among factors to cancer risk. Rodent models for breastcancer provide extensive data on effects of dietary fat and calories,energy balance, body weight gain, and physical activity on tumordevelopment. Analyses of the combined data from many studies have shownclearly that quality and quantity of dietary fat and energy balancecontribute independently to increased mammary gland tumorigenesis. Thesefindings were seen in female rats fed diets high in fat (35-40% ofcalories) compared to rats fed control diets, with approximately 10% ofcalories as fat (Fay and Freedman, 1997, Breast Cancer Res. Treat. 46,215-223). The methods used permit comparison of experimental andepidemiological data, and they may be useful in extrapolating betweenspecies and developing public health recommendations. In addition to thecontributions of lifetime-diet composition, intake, energy balance, andphysical activity to cancer risk, there are questions about the timing andduration of alterations in these factors and about the "dose-response"characteristics of cancer risk to the factors. Endocrine mechanisms may besignificant in mammary gland tumor risk, but experimental andepidemiological data indicate that cancers at other sites, such as colonand liver, also are influenced by the factors listed. Other diet andlifestyle factors that influence energy, or specifically fat, metabolismmay also affect risk for cancers that are promoted by increased intake offat and calories. Studies of separate and interactive effects of dietaryfat, black tea, weight gain, and mammary gland tumorigenesis (Rogers, etal, 1998, Carcinogenesis 19, 1269-1273) have been analyzed. Usingadjustment of carcinogenesis endpoints for body weight, tumor burden, andlatency, they were found to be related to weight gain within treatmentgroups in 2 of 3 experiments.