Weight, physical activity, and nutrition alter cancer risk and carcinogenesis for many cancers, and evidence is accumulating on the effect of these health factors on cancer prognosis and quality of life among cancer survivors. Along with an increase in total energy consumption over the past few decades, a clear shift in the types of nutrients consumed in the American diet has been highlighted. Specifically, the consumption of fructose has increased dramatically, primarily because of increased consumption of beverages that are high in fructose and the consumption of other foods sweetened with sucrose and high-fructose corn syrup (HFCS). High carbohydrate intake has been hypothesized to be a risk factor for pancreatic cancer, possibly mediated by elevated levels of free insulin and insulin-like growth factor-I, and fructose feeding-induces insulin resistance, mainly due to a diminished ability of insulin to suppress hepatic glucose output. However, the association between carbohydrate intake and pancreatic cancer is likely multifactorial, and in addition to insulin resistance, lipids and triglyceride levels have been associated with increased pancreatic cancer risk. We hypothesize that cancer cells themselves may be able to distinguish, and preferentially utilize different carbohydrates, and altered glucose transporter levels have been described in some cancers. This proposal will characterize the potential mechanisms by which different carbohydrates affect pancreatic cancer proliferation, focusing on the role of glucose uptake and transport factors, such as Glut-5.
The second aim will examine the effects of refined carbohydrate administration on tumor growth rates in an animal model of pancreatic cancer. Public Health Relevance Statement: Pancreatic cancer is the fourth leading cause of US death, and despite some improvement in therapy, 5-year survival rate is only 5%, and novel strategies to aid early diagnosis and therapy are urgently needed. The important role that diet, and specifically high refined carbohydrate intake, plays in cancer is increasingly appreciated, and the previously unrecognized proliferative effects of refined fructose in pancreatic cancer that we will investigate are of immediate importance to patients with pancreatic cancer. Our identification of GLUT-5 as a key in the molecular mechanism by which pancreatic cancer cells preferentially utilize fructose may pave the way to novel therapeutic approaches targeting GLUT-5 action in pancreatic cancer.
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