Eleni Oikonomou

Serum C-peptide, IGFBP-1 and IGFBP-2 and risk of colon and rectal cancers in the European Prospective Investigation into Cancer and Nutrition

Western style diets and lifestyles are associated with increasing rates of obesity, diabetes and insulin resistance. Higher circulating insulin levels may modulate cell proliferation and apoptosis either directly or indirectly by increasing the bioactivity of IGF‐I and decreasing the bioactivity of some of its binding proteins. The objective of this study was to determine the association of increasing levels of serum C‐peptide, a biomarker of pancreatic insulin secretion, and IGF binding proteins (IGFBP) ‐1 and ‐2 with colorectal cancer risk in a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 Western European countries. A total of 1,078 colorectal cancer cases were matched (age, date of blood donation, fasting status, gender, study center) to an equal number of control subjects. Relative cancer risks were estimated using conditional logistic regression models. Serum C‐peptide concentration was positively associated with an increased colorectal cancer risk for the highest versus the lowest quintile (OR = 1.56, 95% CI = 1.16–2.09, ptrend < 0.01), which was slightly attenuated after adjustment for BMI and physical activity (OR = 1.37, 95% CI = 1.00–1.88, ptrend = 0.10). When stratified by anatomical site, the cancer risk was stronger in the colon (OR = 1.67, 95% CI = 1.14–2.46, ptrend < 0.01) than in the rectum (OR = 1.42, 95% CI = 0.90–2.25, ptrend = 0.35). The cancer risk estimates were not heterogeneous by gender or fasting status. No clear colorectal cancer risk associations were observed for IGFBP‐1 or ‐2. This large prospective study confirms that hyperinsulinemia, as determined by C‐peptide levels, is associated with an increased colorectal cancer risk.

Plasma and dietary carotenoid, retinol and tocopherol levels and the risk of gastric adenocarcinomas in the European prospective investigation into cancer and nutrition

Despite declining incidence rates, gastric cancer (GC) is a major cause of death worldwide. Its aetiology may involve dietary antioxidant micronutrients such as carotenoids and tocopherols. The objective of this study was to determine the association of plasma levels of seven common carotenoids, their total plasma concentration, retinol and α- and γ-tocopherol, with the risk of gastric adenocarcinoma in a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 countries. A secondary objective was to determine the association of total sum of carotenoids, retinol and α-tocopherol on GCs by anatomical subsite (cardia/noncardia) and histological subtype (diffuse/intestinal). Analytes were measured by high-performance liquid chromatography in prediagnostic plasma from 244 GC cases and 645 controls matched by age, gender, study centre and date of blood donation. Conditional logistic regression models adjusted by body mass index, total energy intake, smoking and Helicobacter pylori infection status were used to estimate relative cancer risks. After an average 3.2 years of follow-up, a negative association with GC risk was observed in the highest vs the lowest quartiles of plasma β-cryptoxanthin (odds ratio (OR)=0.53, 95% confidence intervals (CI)=0.30–0.94, Ptrend=0.006), zeaxanthin (OR=0.39, 95% CI=0.22–0.69, Ptrend=0.005), retinol (OR=0.55, 95% CI=0.33–0.93, Ptrend=0.005) and lipid-unadjusted α-tocopherol (OR=0.59, 95% CI=0.37–0.94, Ptrend=0.022). For all analytes, no heterogeneity of risk estimates or significant associations were observed by anatomical subsite. In the diffuse histological subtype, an inverse association was observed with the highest vs lowest quartile of lipid-unadjusted α-tocopherol (OR=0.26, 95% CI=0.11–0.65, Ptrend=0.003). These results show that higher plasma concentrations of some carotenoids, retinol and α-tocopherol are associated with reduced risk of GC.

Tobacco smoke and bladder cancer-in the European prospective investigation into cancer and nutrition

The purpose of the present study was to investigate the association between smoking and the development of bladder cancer. The study population consisted of 429,906 persons participating in the European Prospective Investigation into Cancer and Nutrition (EPIC), 633 of whom developed bladder cancer during the follow‐up period. An increased risk of bladder cancer was found for both current‐ (incidence rate ratio 3.96, 95% confidence interval: 3.07–5.09) and ex‐ (2.25, 1.74–2.91) smokers, compared to never‐smokers. A positive association with intensity (per 5 cigarettes) was found among current‐smokers (1.18, 1.09–1.28). Associations (per 5 years) were observed for duration (1.14, 1.08–1.21), later age at start (0.75, 0.66–0.85) and longer time since quitting (0.92, 0.86–0.98). Exposure to environmental tobacco smoke (ETS) during childhood increased the risk of bladder cancer (1.38, 1.00–1.90), whereas for ETS exposure as adult no effect was detected. The present study confirms the strong association between smoking and bladder cancer. The indication of a higher risk of bladder cancer for those who start smoking at a young age and for those exposed to ETS during childhood adds to the body of evidence suggesting that children are more sensitive to carcinogens than adults.

Eating out of home: energy, macro- and micronutrient intakes in 10 European countries. The European Prospective Investigation into Cancer and Nutrition

Objectives:To assess the contribution of out-of-home (OH) energy and nutrient intake to total dietary intake, and to compare out- versus in-home nutrient patterns among 27 centres in 10 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.Methods:Between 1995 and 2000, 36 034 participants aged between 35–74 years completed a standardized 24-h dietary recall using a software programme (EPIC-Soft) that recorded the place of food/drink consumption. Eating OH was defined as the consumption of foods and beverages anywhere other than in household premises, irrespective of the place of purchase/preparation. Nutrient intakes were estimated using a standardized nutrient database. Mean intakes were adjusted for age and weighted by season and day of recall.Results:Among women, OH eating contributed more to total fat intake than to intakes of protein and carbohydrates. Among both genders, and particularly in southern Europe, OH eating contributed more to sugar and starch intakes and less to total fibre intake. The contribution of OH eating was also lower for calcium and vitamin C intakes. The composition of diet at home was different from that consumed out of home in southern countries, but was relatively similar in the north.Conclusions:In northern Europe, OH and in-home eating are homogeneous, whereas southern Europeans consider OH eating as a distinctive occasion. In most centres, women selected more fat-rich items when eating out.

Endogenous androgens and risk of epithelial ovarian cancer: results from the European Prospective Investigation into Cancer and Nutrition (EPIC).

Few epidemiologic studies have examined the hypothesis that circulating androgens are involved in the development of ovarian cancer. We investigated the association between prediagnostic serum levels of androgens and sex hormone–binding globulin (SHBG) and ovarian cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition cohort. One hundred and ninety-two ovarian cancer cases and 346 matched controls not using exogenous hormones at baseline blood donation were eligible for the study. Serum levels of testosterone, androstenedione, dehydroepiandrosterone sulfate, and SHBG were measured by direct immunoassays. Free testosterone (fT) was calculated according to mass action laws. Multivariate conditional logistic regression was used to estimate odds ratios adjusted for possible confounders. Overall, there was no association between serum concentrations of androgens or SHBG and ovarian cancer risk. In postmenopausal women, fT concentrations were inversely related to risk [highest versus lowest tertile odds ratio 0.45 (0.24-0.86); Ptrend = 0.01]. Among women diagnosed before the age of 55 years, there was a negative association with SHBG and a positive association with fT and ovarian cancer risk, although these associations were not statistically significant. The present study suggests that circulating androgens and SHBG levels are not strongly associated with ovarian cancer risk, although levels of fT may be associated with an increased risk among women diagnosed at relatively young age. The heterogeneity of results on the associations of fT with ovarian cancer risk in postmenopausal women deserves further investigation. (Cancer Epidemiol Biomarkers Prev 2007;16(1):23–9)

Eating out, weight and weight gain. A cross-sectional and prospective analysis in the context of the EPIC-PANACEA study

Objective:The aim of this study was to examine the association of body mass index (BMI) and weight gain with eating at restaurants and similar establishments or eating at work among 10 European countries of the European Prospective Investigation into Cancer and Nutrition (EPIC) study.Subjects:This study included a representative sample of 24 310 randomly selected EPIC participants.Methods:Single 24-h dietary recalls with information on the place of consumption were collected using standardized procedures between 1995 and 2000. Eating at restaurants was defined to include all eating and drinking occasions at restaurants, cafeterias, bars and fast food outlets. Eating at work included all eating and drinking occasions at the workplace. Associations between eating at restaurants or eating at work and BMI or annual weight changes were assessed using sex-specific linear mixed-effects models, controlling for potential confounders.Results:In southern Europe energy intake at restaurants was higher than intake at work, whereas in northern Europe eating at work appeared to contribute more to the mean daily intake than eating at restaurants. Cross-sectionally, eating at restaurants was found to be positively associated with BMI only among men (β=+0.24, P=0.003). Essentially no association was found between BMI and eating at work among both genders. In a prospective analysis among men, eating at restaurants was found to be positively, albeit nonsignificantly, associated with weight gain (β=+0.05, P=0.368). No association was detected between energy intake at restaurants and weight changes, controlling for total energy intake.Conclusion:Among men, eating at restaurants and similar establishments was associated with higher BMI and possibly weight gain.

Red Meat, Dietary Nitrosamines, and Heme Iron and Risk of Bladder Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Background: Previous epidemiologic studies found inconsistent results for the association between red meat intake, nitrosamines [NDMA: N-nitrosodimethylamine, and ENOC (endogenous nitroso compounds)], and the risk of bladder cancer. We investigated the association between red meat consumption, dietary nitrosamines, and heme iron and the risk of bladder cancer among participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: Data on food consumption and complete follow-up for cancer occurrence were available for a total of 481,419 participants, recruited in 10 European countries. Estimates of HRs were obtained by proportional hazard models, stratified by age at recruitment, gender, and study center and adjusted for total energy intake, smoking status, lifetime intensity of smoking, duration of smoking, educational level, and BMI. Results: After a mean follow-up of 8.7 years, 1,001 participants were diagnosed with bladder cancer. We found no overall association between intake of red meat (log2 HR: 1.06; 95% CI: 0.99–1.13), nitrosamines (log2 HR: 1.09; 95% CI: 0.92–1.30 and HR: 0.98; 95% CI: 0.92–1.05 for ENOC and NDMA, respectively) or heme iron (log2 HR: 1.05; 95 CI: 0.99–1.12) and bladder cancer risk. The associations did not vary by sex, high- versus low-risk bladder cancers, smoking status, or occupation (high vs. low risk). Conclusions: Our findings do not support an effect of red meat intake, nitrosamines (endogenous or exogenous), or heme iron intake on bladder cancer risk. Cancer Epidemiol Biomarkers Prev; 20(3); 555–9. ©2011 AACR.

A bivariate measurement error model for nitrogen and potassium intakes to evaluate the performance of regression calibration in the European Prospective Investigation into Cancer and Nutrition study.

Objectives:Within the European Prospective Investigation into Cancer and Nutrition (EPIC) study, the performance of 24-h dietary recall (24-HDR) measurements as reference measurements in a linear regression calibration model is evaluated critically at the individual (within-centre) and aggregate (between-centre) levels by using unbiased estimates of urinary measurements of nitrogen and potassium intakes.Methods:Between 1995 and 1999, 1072 study subjects (59% women) from 12 EPIC centres volunteered to collect 24-h urine samples. Log-transformed questionnaire, 24-HDR and urinary measurements of nitrogen and potassium intakes were analysed in a multivariate measurement error model to estimate the validity of coefficients and error correlations in self-reported dietary measurements. In parallel, correlations between means of 24-HDR and urinary measurements were computed. Linear regression calibration models were used to estimate the regression dilution (attenuation) factors.Results:After adjustment for sex, centre, age, body mass index and height, the validity coefficients for 24-HDRs were 0.285 (95% confidence interval: 0.194, 0.367) and 0.371 (0.291, 0.446) for nitrogen and potassium intakes, respectively. The attenuation factors estimated in a linear regression calibration model were 0.368 (0.228, 0.508) for nitrogen and 0.500 (0.361, 0.639) for potassium intakes; only the former was different from the estimate obtained using urinary measurements in the measurement error model. The aggregate-level correlation coefficients between means of urinary and 24-HDR measurements were 0.838 (0.637, 0.932) and 0.756 (0.481, 0.895) for nitrogen and potassium intakes, respectively.Conclusions:This study suggests that 24-HDRs can be used as reference measurements at the individual and aggregate levels for potassium intake, whereas, for nitrogen intake, good performance is observed for between-centre calibration, but some limitations are apparent at the individual level.

Consumption of predefined 'Nordic' dietary items in ten European countries - an investigation in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

OBJECTIVE Health-beneficial effects of adhering to a healthy Nordic diet index have been suggested. However, it has not been examined to what extent the included dietary components are exclusively related to the Nordic countries or if they are part of other European diets as well, suggesting a broader preventive potential. The present study describes the intake of seven a priori defined healthy food items (apples/pears, berries, cabbages, dark bread, shellfish, fish and root vegetables) across ten countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) and examines their consumption across Europe. DESIGN Cross-sectional study. A 24 h dietary recall was administered through a software program containing country-specific recipes. Sex-specific mean food intake was calculated for each centre/country, as well as percentage of overall food groups consumed as healthy Nordic food items. All analyses were weighted by day and season of data collection. SETTING Multi-centre, European study. SUBJECTS Persons (n 36 970) aged 35-74 years, constituting a random sample of 519 978 EPIC participants. RESULTS The highest intakes of the included diet components were: cabbages and berries in Central Europe; apples/pears in Southern Europe; dark bread in Norway, Denmark and Greece; fish in Southern and Northern countries; shellfish in Spain; and root vegetables in Northern and Central Europe. Large inter-centre variation, however, existed in some countries. CONCLUSIONS Dark bread, root vegetables and fish are strongly related to a Nordic dietary tradition. Apples/pears, berries, cabbages, fish, shellfish and root vegetables are broadly consumed in Europe, and may thus be included in regional public health campaigns.

Specific food group combinations explaining the variation in intakes of nutrients and other important food components in the European Prospective Investigation into Cancer and Nutrition : an application of the reduced rank regression method

Objective:To identify combinations of food groups that explain as much variation in absolute intakes of 23 key nutrients and food components as possible within the country-specific populations of the European Prospective Investigation into Cancer and Nutrition (EPIC).Subjects/Methods:The analysis covered single 24-h dietary recalls (24-HDR) from 36 034 subjects (13 025 men and 23 009 women), aged 35–74 years, from all 10 countries participating in the EPIC study. In a set of 39 food groups, reduced rank regression (RRR) was used to identify those combinations (RRR factors) that explain the largest proportion of variation in intake of 23 key nutrients and food components, namely, proteins, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, cholesterol, sugars (sum of mono- and disaccharides), starch, fibre, alcohol, calcium, iron, potassium, phosphorus, magnesium, vitamin D, β-carotene, retinol and vitamins E, B1, B2, B6, B12 and C (RRR responses). Analyses were performed at the country level and for all countries combined.Results:In the country-specific analyses, the first RRR factor explained a considerable proportion of the total nutrient intake variation in all 10 countries (27.4–37.1%). The subsequent RRR factors were much less important in explaining the variation (⩽6%). Strong similarities were observed for the first country-specific RRR factor between the individual countries, largely characterized by consumption of bread, vegetable oils, red meat, milk, cheese, potatoes, margarine and processed meat. The highest explained variation was seen for protein, potassium, phosphorus and magnesium (50–70%), whereas sugars, β-carotene, retinol and alcohol were only marginally explained (⩽5%). The explained proportion of the other nutrients ranged between these extremes.Conclusions:A combination of food groups was identified that explained a considerable proportion of the nutrient intake variation in 24-HDRs in every country-specific EPIC population in a similar manner. This indicates that, despite the large variability in food and nutrient intakes reported in the EPIC, the variance of intake of important nutrients is explained, to a large extent, by similar food group combinations across countries.