The dietary glycemic index and its implications in cancer risk, insulin-like growth factors and oxidative stress

Abstract

This thesis is an investigation of the role of the dietary glycemic index (GI) in endometrial and ovarian cancer risk and two potential mechanisms, related to insulin-like growth factors (IGF) and oxidative stress. The dietary GI is a measure of the foods' potential for blood glucose rises and the higher the GI the higher the blood glucose and insulin responses. In studies 1 and 2, the average daily GI of the diet was assessed in subjects with newly diagnosed endometrial cancer, those with ovarian cancer and in healthy controls. These case-control studies found positive associations between dietary GI and risk of endometrial and ovarian cancer (Odds Ratios, 2.1 and 1.7 respectively, for highest versus lowest GI quintile). These and other emerging studies indicate a possible link between high GI diets and cancer risk suggesting a potential role of glucose and insulin in carcinogenesis and a possible protective effect of low GI diets. A potential mechanism of cancer promotion, affected by insulin, has been linked to high IGF-I and lower IGF binding proteins (IGFBP) levels. Study 3 and 4 investigated the potential role in cancer risk of IGF components in blood samples of subsets of the endometrial and ovarian cancer studies. These case-control studies did not find any significant associations of IGF-I with endometrial or ovarian cancer risk, however, IGFBP-1 was directly and IGFBP-3 inversely associated with endometrial and ovarian cancer risk, respectively. Oxidative stress, generated also by the normal pathways of carbohydrate metabolism, has been implicated in cancer initiation. Study 5 proposed that the lower blood glucose levels after consumption of low GI foods would induce lower oxidative stress than with high GI foods. This study showed a lack of effects of the dietary GI on antioxidant status and oxidative damage possibly due to the small glycemic excursions and short study duration. In conclusion, the dietary GI may be directly related to endometrial and ovarian cancer risk, however, the two proposed mechanisms (increased IGF-I and oxidative stress) did not show clear results in our studies. Larger studies and of longer duration may be required to detect possible significant effects.