DIET AND ENDOMETRIAL CANCER Insulin related factors

There is accumulating evidence that insulin resistance and hyperinsulinemia are involved in the etiology of endometrial cancer. Dietary intake can influence insulin levels especially among individuals who are already insulin resistant. Coffee drinking has been reported to have beneficial effects on insulin sensitivity. Glycemic index and load are concepts developed to quantify the glycemic response and insulin demand to carbohydrates in different foods. A moderate alcohol intake has been shown to improve insulin sensitivity whereas a higher intake has been shown to increase estrogen levels which unbalanced by progesterone may increase the risk of endometrial cancer. In the analyses we used data from the Swedish Mammography Cohort, a population-based prospective cohort study including over 60 000 women, born 1914-48, among whom 689 endometrioid adenocarcinoma cases were diagnosed through 2007 (17.6 years of follow-up). We examined the association between coffee consumption, carbohydrate intake, glycemic index, glycemic load and alcohol consumption at baseline 1987-90 and in 1997 and endometrial cancer risk using Cox proportional hazards models. To quantitatively summarize the association between alcohol, diabetes and the risk of endometrial cancer, we conducted meta-analyses of published studies. In the metaanalyses we identified studies by literature searches of the databases PubMed and Embase and by searching the reference lists of relevant articles. We summarized the relative risks (RRs) with 95% confidence intervals (CIs) using random-effects models and in the meta-analysis of alcohol also with a dose-response random-effect metaregression model. Drinking four cups or more of coffee per day was overall associated with a 25% decreased risk of endometrial cancer as compared to one cup of coffee or less per day. The association seemed to be largely confined to overweight and obese women. We observed no overall association between carbohydrate intake, glycemic index, or glycemic load and the incidence of endometrial cancer. Among overweight and obese women with low physical activity, who completed the questionnaire in 1997, carbohydrate intake and glycemic load were positively related to endometrial cancer risk. In this subgroup, the RRs comparing extreme quartiles were 1.90 (95% CI 0.844.31) for carbohydrate intake and 2.99 (95% CI 1.17-7.67) for glycemic load. We observed no association between alcohol and endometrial cancer risk in the Swedish elderly study population with a generally low consumption. However, in the meta-analysis of alcohol and endometrial cancer incidence based on 7 cohort studies, we observed a statistically significant inverse association with low consumption as compared to non-drinkers and a higher risk associated with 2 drinks or more per day. In the meta-analysis of diabetes and endometrial cancer, based on 16 studies, we found that diabetes was significantly associated with an increased risk of endometrial cancer (summary RR 2.10 95% CI 1.75-2.53). The meta-analysis of type 1 diabetes and endometrial cancer was based on three studies and also found a significant positive association. In conclusion, our results indicate that dietary factors related to insulin resistance and hyperinsulinemia as well as diabetes may play an important role in the development of endometrial cancer. Hyperinsulinemia may stimulate proliferation of endometrial cells both through insulin-like growth factors and by increased levels of unbound estrogens. LIST OF PUBLICATIONS I. Emilie Friberg, Nicola Orsini, Christos S. Mantzoros and Alicja Wolk. Coffee drinking and risk of endometrial cancer: A population-based prospective cohort study. International Journal of Cancer (in press) II. Susanna C. Larsson, Emilie Friberg and Alicja Wolk. Carbohydrate intake, glycemic index, and glycemic load in relation to risk of endometrial cancer: A prospective study of Swedish women. International Journal of Cancer 2007;120(5):1103-7 III. Emilie Friberg and Alicja Wolk. Long-term Alcohol Consumption and Risk of Endometrial Cancer Incidence: A Prospective Cohort Study. Cancer Epidemiol Biomarkers Prev. 2009;18(1):355-8 IV. Emilie Friberg, Nicola Orsini, Christos S. Mantzoros and Alicja Wolk. Alcohol consumption and risk of endometrial cancer: A Meta-Analysis of prospective studies. Submitted V. Emilie Friberg, Nicola Orsini, Christos S. Mantzoros, and Alicja Wolk. Diabetes mellitus and risk of endometrial cancer: A Meta-Analysis. Diabetologia 2007;50(7):1365-74 RELATED PUBLICATIONS Emilie Friberg, Christos S. Mantzoros, and Alicja Wolk. Diabetes mellitus and risk of endometrial cancer: A Population-based prospective cohort study. Cancer Epidemiol Biomarkers Prev. 2007;16(2):276-80 Emilie Friberg, Christos S. Mantzoros and Alicja Wolk. Physical activity and risk of endometrial cancer: A population-based prospective cohort study. Cancer Epidemiol Biomarkers Prev. 2006;15(11):2136-40