Dietary sugar, glycemic load, and pancreatic cancer risk in a prospective study

Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20852, USA.
JNCI Journal of the National Cancer Institute (Impact Factor: 12.58). 10/2002; 94(17):1293-300.
Source: PubMed


Evidence from both animal and human studies suggests that abnormal glucose metabolism plays an important role in pancreatic carcinogenesis. We investigated whether diets high in foods that increase postprandial glucose levels are associated with an increased risk of pancreatic cancer.
In a cohort of U.S. women (n = 88 802) participating in the Nurses' Health Study, 180 case subjects with pancreatic cancer were diagnosed during 18 years of follow-up. We used frequency of intake of individual foods as reported on a food-frequency questionnaire in 1980 to calculate sucrose, fructose, and carbohydrate intakes; glycemic index (postprandial blood glucose response as compared with a reference food); and glycemic load (glycemic index multiplied by carbohydrate content). Analyses of relative risk (RR) were performed by using multivariable Cox proportional hazards models to adjust for potential confounders. All statistical tests were two-sided.
Carbohydrate and sucrose intake were not associated with overall pancreatic cancer risk in this cohort. A statistically nonsignificant 53% increase in risk of pancreatic cancer (RR = 1.53, 95% confidence interval [CI] = 0.96 to 2.45) was observed among women with a high glycemic load intake, and a similar association was observed for fructose intake (RR = 1.57, 95% CI = 0.95 to 2.57). The associations of glycemic load and fructose intakes with pancreatic cancer risk were most apparent among women with elevated body mass index (>or=25 kg/m(2)) or with low physical activity. Among women who were both overweight and sedentary, a high glycemic load was associated with an RR of 2.67 (95% CI = 1.02 to 6.99; highest versus lowest quartile of intake; P for trend =.03), and high fructose was associated with an RR of 3.17 (95% CI = 1.13 to 8.91; P for trend =.04).
Our data support other findings that impaired glucose metabolism may play a role in pancreatic cancer etiology. A diet high in glycemic load may increase the risk of pancreatic cancer in women who already have an underlying degree of insulin resistance.

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Available from: Graham A Colditz, Dec 31, 2013
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    • "Although pancreatic cancer is difficult to detect in its early stages, several known risk factors exist, with smoking being the most well-documented etiologic agent [2]. Several other risk factors include age, diets high in fat [3], excessive alcohol consumption [4], diabetes mellitus [5], and chronic pancreatitis [6]. Common chemotherapeutic treatments have had little success in improving survival rates or restraining the highly metastatic malignancies [7] with the median survival rate of less than six months and surgical resection as the only effective treatment [8]. "
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    ABSTRACT: PPARβ/δ is a ligand-activated transcription factor that regulates various cellular functions via induction of target genes directly or in concert with its associated transcriptional repressor, BCL-6. Matrix remodeling proteinases are frequently over-expressed in pancreatic cancer and are involved with metastasis. The present study tested the hypothesis that PPARβ/δ is expressed in human pancreatic cancer cells and that its activation could regulate MMP-9, decreasing cancer cells ability to transverse the basement membrane. In human pancreatic cancer tissue there was significantly higher expression of MMP-9 and PPARβ/δ, and lower levels of BCL-6 mRNA. PPARβ/δ activation reduced the TNF α -induced expression of various genes implicated in metastasis and reduced the invasion through a basement membrane in cell culture models. Through the use of short hairpin RNA inhibitors of PPARβ/δ, BCL-6, and MMP-9, it was evident that PPARβ/δ was responsible for the ligand-dependent effects whereas BCL-6 dissociation upon GW501516 treatment was ultimately responsible for decreasing MMP-9 expression and hence invasion activity. These results suggest that PPARβ/δ plays a role in regulating pancreatic cancer cell invasion through regulation of genes via ligand-dependent release of BCL-6 and that activation of the receptor may provide an alternative therapeutic method for controlling migration and metastasis.
    PPAR Research 05/2013; 2013(17):121956. DOI:10.1155/2013/121956 · 1.64 Impact Factor
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    • "M and F GL (+) Larsson et al., 2006 61, 433 F NA Pancreatic cancer Michaud et al., 2002 88, 802 F NA Johnson et al., 2005 41, 836 F (PM) NA Patel et al., 2007 124, 907 M NA Heinan et al., 2008 120, 852F&M NA are currently limited. Therefore, low-GI and -GL diets show promise for the prevention and treatment of chronic diseases. "
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    ABSTRACT: The persistence of an epidemic of obesity, coronary heart disease and type 2 diabetes suggests that new nutritional strategies are needed if the epidemic is to be overcome. A promising nutritional approach suggested by this thematic review is carbohydrate restriction. Under conditions of carbohydrate restriction, fuel sources shift from glucose and fatty acids to fatty acids and ketones, and that ad libitum–fed carbohydrate-restricted diets lead to appetite reduction, weight loss, and improvement in surrogate markers of cardiovascular disease. Recent researches focus on the debate among professionals regarding the use of the glycemic index (GI) for meal planning. However, evidence from individual trials about benefits and risks of these diets to achieve weight loss and modify cardiovascular risk factors is preliminary. In epidemic studies, there is limited evidence that a low GI diet is beneficial for a reduced risk of developing diabetes or prevalence of insulin resistance, weight loss or satiety, and other cancers. The GI can be used as an adjunct for the fine tuning of postprandial blood glucose responses, particularly in diabetic patients. Other food/meal-planning interventions have been shown to be more effective than the use of the GI.
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    • "A high habitual dietary GI seems to favour overweight (Ludwig, 2003), and direct associations between high GI and/or GL have been found for different types of diseases, including non-insulin-dependent diabetes mellitus, obesity, cardiovascular disease and cancer (Du et al., 2006; Barclay et al., 2008), but results are still contradictory. It seems that for certain diseases, the association with dietary GL is only present among certain subgroups, such as overweight (Liu et al., 2002; Beulens et al., 2007) and sedentary individuals (Michaud et al., 2002) or in pre-menopausal women with a body mass index (BMI) 425 kg/m 2 (Cho et al., 2003). "
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    ABSTRACT: To describe dietary glycaemic index (GI) and glycaemic load (GL) values in the population participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study according to food groups, nutrients and lifestyle characteristics. Single 24-h dietary recalls (24-HDRs) from 33 566 subjects were used to calculate dietary GI and GL, and an ad hoc database was created as the main reference source. Mean GI and GL intakes were adjusted for age, total energy intake, height and weight, and were weighted by season and day of recall. GI was the lowest in Spain and Germany, and highest in the Netherlands, United Kingdom and Denmark for both genders. In men, GL was the lowest in Spain and Germany and highest in Italy, whereas in women, it was the lowest in Spain and Greece and highest in the UK health-conscious cohort. Bread was the largest contributor to GL in all centres (15-45%), but it also showed the largest inter-individual variation. GL, but not GI, tended to be lower in the highest body mass index category in both genders. GI was positively correlated with starch and intakes of bread and potatoes, whereas it was correlated negatively with intakes of sugar, fruit and dairy products. GL was positively correlated with all carbohydrate components and intakes of cereals, whereas it was negatively correlated with fat and alcohol and with intakes of wine, with large variations across countries. GI means varied modestly across countries and genders, whereas GL means varied more, but it may possibly act as a surrogate of carbohydrate intake.
    European journal of clinical nutrition 11/2009; 63 Suppl 4(Suppl 4):S188-205. DOI:10.1038/ejcn.2009.81 · 2.71 Impact Factor
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