High-Fructose Corn Syrup Enhances Intestinal Tumor Growth in Mice

Excessive consumption of beverages sweetened with high-fructose corn syrup (HFCS) is associated with obesity and with an increased risk of colorectal cancer. Whether HFCS contributes directly to tumorigenesis is unclear. We investigated the effects of daily oral administration of HFCS in APC mutant mice, which are predisposed to develop intestinal tumors. The HFCS-treated mice showed a dramatic increase in tumor size and tumor grade in the absence of obesity or metabolic syndrome. HFCS increased the levels of fructose and glucose in the intestinal lumen and serum, respectively, and the tumors absorbed both sugars. Within the tumors, fructose was converted to fructose-1-phosphate, leading to activation of glycolysis and increased synthesis of fatty acids that support tumor growth. These mouse studies support the hypothesis that the combination of dietary glucose and fructose, even at a moderate dose, can enhance tumorigenesis. Overall design: We investigated tumor and small intestines in APC mutant mice, which are predisposed to develop intestinal tumors.

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Goncalves MD, Lu C, Tutnauer J, Hartman TE, Hwang SK, Murphy CJ, Pauli C, Morris R, Taylor S, Bosch K, Yang S, Wang Y, Van Riper J, Lekaye HC, Roper J, Kim Y, Chen Q, Gross SS, Rhee KY, Cantley LC, Yun J