Cross-Sectional Associations of Objectively Measured Physical Activity, Cardiorespiratory Fitness and Anthropometry in European Adults

Objective: To quantify the independent associations between objectively measured physical activity (PA), cardiorespiratory fitness (CRF), and anthropometry in European men and women. Methods: 2,056 volunteers from 12 centers across Europe were fitted with a heart rate and movement sensor at 2 visits 4 months apart for a total of 8 days. CRF (ml/kg/min) was estimated from an 8 minute ramped step test. A cross-sectional analysis of the independent associations between objectively measured PA (m/s(2)/d), moderate and vigorous physical activity (MVPA) (% time/d), sedentary time (% time/d), CRF, and anthropometry using sex stratified multiple linear regression was performed. Results: In mutually adjusted models, CRF, PA, and MVPA were inversely associated with all anthropometric markers in women. In men, CRF, PA, and MVPA were inversely associated with BMI, whereas only CRF was significantly associated with the other anthropometric markers. Sedentary time was positively associated with all anthropometric markers, however, after adjustment for CRF significant in women only. Conclusion: CRF, PA, MVPA, and sedentary time are differently associated with anthropometric markers in men and women. CRF appears to attenuate associations between PA, MVPA, and sedentary time. These observations may have implications for prevention of obesity

Cross-Sectional Associations of Objectively Measured Physical Activity, Cardiorespiratory Fitness and Anthropometry in European Adults

Objective: To quantify the independent associations between objectively measured physical activity (PA), cardiorespiratory fitness (CRF), and anthropometry in European men and women. Methods: 2,056 volunteers from 12 centers across Europe were fitted with a heart rate and movement sensor at 2 visits 4 months apart for a total of 8 days. CRF (ml/kg/min) was estimated from an 8 minute ramped step test. A cross-sectional analysis of the independent associations between objectively measured PA (m/s(2)/d), moderate and vigorous physical activity (MVPA) (% time/d), sedentary time (% time/d), CRF, and anthropometry using sex stratified multiple linear regression was performed. Results: In mutually adjusted models, CRF, PA, and MVPA were inversely associated with all anthropometric markers in women. In men, CRF, PA, and MVPA were inversely associated with BMI, whereas only CRF was significantly associated with the other anthropometric markers. Sedentary time was positively associated with all anthropometric markers, however, after adjustment for CRF significant in women only. Conclusion: CRF, PA, MVPA, and sedentary time are differently associated with anthropometric markers in men and women. CRF appears to attenuate associations between PA, MVPA, and sedentary time. These observations may have implications for prevention of obesity

Methylome Analysis and Epigenetic Changes Associated with Menarcheal Age

Reproductive factors have been linked to both breast cancer and DNA methylation, suggesting methylation as an important mechanism by which reproductive factors impact on disease risk. However, few studies have investigated the link between reproductive factors and DNA methylation in humans. Genome-wide methylation in peripheral blood lymphocytes of 376 healthy women from the prospective EPIC study was investigated using LUminometric Methylation Assay (LUMA). Also, methylation of 458877 CpG sites was additionally investigated in an independent group of 332 participants of the EPIC-Italy sub-cohort, using the Infinium HumanMethylation 450 BeadChip. Multivariate logistic regression and linear models were used to investigate the association between reproductive risk factors and genome wide and CpG-specific DNA methylation, respectively. Menarcheal age was inversely associated with global DNA methylation as measured with LUMA. For each yearly increase in age at menarche, the risk of having genome wide methylation below median level was increased by 32% (OR: 1.32, 95% CI: 1.14-1.53). When age at menarche was treated as a categorical variable, there was an inverse dose-response relationship with LUMA methylation levels (OR12-14vs.<= 11 yrs: 1.78, 95% CI: 1.01-3.17 and OR >= 15vs.<= 11 yrs: 4.59, 95% CI: 2.04-10.33; P for trend<0.0001). However, average levels of global methylation as measured by the Illumina technology were not significantly associated with menarcheal age. In locus by locus comparative analyses, only one CpG site had significantly different methylation depending on the menarcheal age category examined, but this finding was not replicated by pyrosequencing in an independent data set. This study suggests a link between age at menarche and genome wide DNA methylation, and the difference in results between the two arrays suggests that repetitive element methylation has a role in the association. Epigenetic changes may be modulated by menarcheal age, or the association may be a mirror of other important changes in early life that have a detectable effect on both methylation levels and menarcheal age

Nutrient Patterns and Their Food Sources in an International Study Setting : Report from the EPIC Study

Background: Compared to food patterns, nutrient patterns have been rarely used particularly at international level. We studied, in the context of a multi-center study with heterogeneous data, the methodological challenges regarding pattern analyses. Methodology/Principal Findings: We identified nutrient patterns from food frequency questionnaires (FFQ) in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study and used 24-hour dietary recall (24-HDR) data to validate and describe the nutrient patterns and their related food sources. Associations between lifestyle factors and the nutrient patterns were also examined. Principal component analysis (PCA) was applied on 23 nutrients derived from country-specific FFQ combining data from all EPIC centers (N = 477,312). Harmonized 24-HDRs available for a representative sample of the EPIC populations (N = 34,436) provided accurate mean group estimates of nutrients and foods by quintiles of pattern scores, presented graphically. An overall PCA combining all data captured a good proportion of the variance explained in each EPIC center. Four nutrient patterns were identified explaining 67% of the total variance: Principle component (PC) 1 was characterized by a high contribution of nutrients from plant food sources and a low contribution of nutrients from animal food sources; PC2 by a high contribution of micro-nutrients and proteins; PC3 was characterized by polyunsaturated fatty acids and vitamin D; PC4 was characterized by calcium, proteins, riboflavin, and phosphorus. The nutrients with high loadings on a particular pattern as derived from country-specific FFQ also showed high deviations in their mean EPIC intakes by quintiles of pattern scores when estimated from 24-HDR. Center and energy intake explained most of the variability in pattern scores. Conclusion/Significance: The use of 24-HDR enabled internal validation and facilitated the interpretation of the nutrient patterns derived from FFQs in term of food sources. These outcomes open research opportunities and perspectives of using nutrient patterns in future studies particularly at international level

Dietary Intake of Acrylamide and Epithelial Ovarian Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort

Acrylamide, classified in 1994 by the International Agency for Research on Cancer (IARC) as “probably carcinogenic” to humans, was discovered in 2002 in some heat-treated, carbohydrate-rich foods. The association between dietary acrylamide intake and epithelial ovarian cancer risk (EOC) has been previously studied in one case-control and three prospective cohort studies which obtained inconsistent results and could not further examine histologic subtypes other than serous EOC. The present study was carried out in the European Prospective Investigation into Cancer and Nutrition (EPIC) subcohort of women (n = 325,006). Multivariate Cox proportional hazards models were used to assess the association between questionnaire-based acrylamide intake and EOC risk. Acrylamide was energy-adjusted using the residual method and was evaluated both as a continuous variable (per 10 mu g/d) and in quintiles; when subgroups by histologic EOC subtypes were analyzed, acrylamide intake was evaluated in quartiles. During a mean follow-up of 11 years, 1,191 incident EOC cases were diagnosed. At baseline, the median acrylamide intake in EPIC was 21.3 mu g/d. No associations and no evidence for a dose-response were observed between energy-adjusted acrylamide intake and EOC risk (HR10 mu(g/d), 1.02; 95% CI, 0.96-1.09; HRQ5vsQ1, 0.97; 95% CI, 0.76-1.23). No differences were seen when invasive EOC subtypes (582 serous, 118 endometrioid, and 79 mucinous tumors) were analyzed separately. This study did not provide evidence that acrylamide intake, based on food intake questionnaires, was associated with risk for EOC in EPIC. Additional studies with more reliable estimates of exposure based on biomarkers may be needed. (C) 2014 AACR

The Associations of Advanced Glycation End Products and Its Soluble Receptor with Pancreatic Cancer Risk: A Case-Control Study within the Prospective EPIC Cohort

Background: Advanced glycation end products (AGE) and their receptors (RAGE) have been implicated in cancer development through their proinflammatory capabilities. However, prospective data on their association with cancer of specific sites, including pancreatic cancer, are limited. Methods: Prediagnostic blood levels of the AGE product Ne-(carboxymethyl) lysine (CML) and the endogenous secreted receptor for AGE (esRAGE) were measured using ELISA in 454 patients with exocrine pancreatic cancer and individually matched controls within the European Prospective Investigation into Cancer and Nutrition (EPIC). Pancreatic cancer risk was estimated by calculating ORs with corresponding 95% confidence intervals (CI). Results: Elevated CML levels tended to be associated with a reduction in pancreatic cancer risk [OR = 0.57 (95% CI, 0.32-1.01) comparing highest with lowest quintile), whereas no association was observed for esRAGE (OR = 0.98; 95% CI, 0.62-1.54). Adjustments for body mass index and smoking attenuated the inverse associations of CML with pancreatic cancer risk (OR = 0.78; 95% CI, 0.41-1.49). There was an inverse association between esRAGE and risk of pancreatic cancer for cases that were diagnosed within the first 2 years of follow-up [OR = 0.46 (95% CI, 0.22-0.96) for a doubling in concentration], whereas there was no association among those with a longer follow-up (OR = 1.11; 95% CI, 0.88-1.39; P-interaction = 0.002). Conclusions and Impact: Our results do not provide evidence for an association of higher CML or lower esRAGE levels with risk of pancreatic cancer. The role of AGE/RAGE in pancreatic cancer would benefit from further investigations. Cancer Epidemiol Biomarkers Prev; 21(4); 619-28. (C) 2012 AACR

Coffee and tea consumption and the risk of ovarian cancer: a prospective cohort study and updated meta-analysis

Background: In 2007 the World Cancer Research Fund Report concluded that there was limited and inconsistent evidence for an effect of coffee and tea consumption on the risk of epithelial ovarian cancer (EOC). Objective: In the European Prospective Investigation into Cancer and Nutrition (EPIC), we aimed to investigate whether coffee intakes, tea intakes, or both are associated with the risk of EOC. Design: All women participating in the EPIC (n = 330,849) were included in this study. Data on coffee and tea consumption were collected through validated food-frequency questionnaires at baseline. HRs and 95% CIs were estimated by using Cox proportional hazards models. Furthermore, we performed an updated meta-analysis of all previous prospective studies until April 2011 by comparing the highest and lowest coffee- and tea-consumption categories as well as by using dose-response random-effects meta-regression analyses. Results: During a median follow-up of 11.7 y, 1244 women developed EOC. No association was observed between the risk of EOC and coffee consumption [HR: 1.05 (95% CI: 0.75, 1.46) for the top quintile compared with no intake] or tea consumption [HR: 1.07 (95% Cl: 0.78, 1.45) for the top quintile compared with no intake]. This lack of association between coffee and tea intake and EOC risk was confirmed by the results of our meta-analysis. Conclusion: Epidemiologic studies do not provide sufficient evidence to support an association between coffee and tea consumption and risk of ovarian cancer. Am J Clin Nutr 2012;95:1172-81

Dietary total antioxidant capacity and gastric cancer risk in the European prospective investigation into cancer and nutrition study

A high intake of dietary antioxidant compounds has been hypothesized to be an appropriate strategy to reduce gastric cancer (GC) development. We investigated the effect of dietary total antioxidant capacity (TAC) in relation to GC in the European Prospective Investigation into Cancer (EPIC) study including 23 centers in 10 European countries. A total of 521,457 subjects (153,447 men) aged mostly 3570 years old, were recruited largely between 1992 and 1998. Ferric reducing antioxidant potential (FRAP) and total radical-trapping antioxidant parameter (TRAP), measuring reducing and chain-breaking antioxidant capacity were used to measure dietary TAC from plant foods. Dietary antioxidant intake is associated with a reduction in the risk of GC for both FRAP (adjusted HR 0.66; 95%CI (0.460.95) and TRAP (adjusted HR 0.61; 95%CI (0.430.87) (highest vs. lowest quintile). The association was observed for both cardia and noncardia cancers. A clear effect was observed in smokers with a significant reduction in GC risk for the fifth quintile of intake for both assays (highest vs. lowest quintile: adjusted HR 0.41; 95%CI (0.220.76) p for trend <0.001 for FRAP; adjusted HR 0.52; 95%CI (0.280.97) p for trend <0.001 for TRAP) but not in nonsmokers. In former smokers, the association with FRAP intake was statistically significant (highest vs. lowest quintile: adjusted HR 0.4; 95%CI (0.210.75) p < 0.05); no association was observed for TRAP. Dietary antioxidant capacity intake from different sources of plant foods is associated with a reduction in the risk of GC

Nutrient Patterns and Their Food Sources in an International Study Setting: Report from the EPIC Study

Background: Compared to food patterns, nutrient patterns have been rarely used particularly at international level. We studied, in the context of a multi-center study with heterogeneous data, the methodological challenges regarding pattern analyses. Methodology/Principal Findings: We identified nutrient patterns from food frequency questionnaires (FFQ) in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study and used 24-hour dietary recall (24-HDR) data to validate and describe the nutrient patterns and their related food sources. Associations between lifestyle factors and the nutrient patterns were also examined. Principal component analysis (PCA) was applied on 23 nutrients derived from country-specific FFQ combining data from all EPIC centers (N = 477,312). Harmonized 24-HDRs available for a representative sample of the EPIC populations (N = 34,436) provided accurate mean group estimates of nutrients and foods by quintiles of pattern scores, presented graphically. An overall PCA combining all data captured a good proportion of the variance explained in each EPIC center. Four nutrient patterns were identified explaining 67% of the total variance: Principle component (PC) 1 was characterized by a high contribution of nutrients from plant food sources and a low contribution of nutrients from animal food sources; PC2 by a high contribution of micro-nutrients and proteins; PC3 was characterized by polyunsaturated fatty acids and vitamin D; PC4 was characterized by calcium, proteins, riboflavin, and phosphorus. The nutrients with high loadings on a particular pattern as derived from country-specific FFQ also showed high deviations in their mean EPIC intakes by quintiles of pattern scores when estimated from 24-HDR. Center and energy intake explained most of the variability in pattern scores. Conclusion/Significance: The use of 24-HDR enabled internal validation and facilitated the interpretation of the nutrient patterns derived from FFQs in term of food sources. These outcomes open research opportunities and perspectives of using nutrient patterns in future studies particularly at international level

Dietary total antioxidant capacity and gastric cancer risk in the European prospective investigation into cancer and nutrition study

A high intake of dietary antioxidant compounds has been hypothesized to be an appropriate strategy to reduce gastric cancer (GC) development. We investigated the effect of dietary total antioxidant capacity (TAC) in relation to GC in the European Prospective Investigation into Cancer (EPIC) study including 23 centers in 10 European countries. A total of 521,457 subjects (153,447 men) aged mostly 3570 years old, were recruited largely between 1992 and 1998. Ferric reducing antioxidant potential (FRAP) and total radical-trapping antioxidant parameter (TRAP), measuring reducing and chain-breaking antioxidant capacity were used to measure dietary TAC from plant foods. Dietary antioxidant intake is associated with a reduction in the risk of GC for both FRAP (adjusted HR 0.66; 95%CI (0.460.95) and TRAP (adjusted HR 0.61; 95%CI (0.430.87) (highest vs. lowest quintile). The association was observed for both cardia and noncardia cancers. A clear effect was observed in smokers with a significant reduction in GC risk for the fifth quintile of intake for both assays (highest vs. lowest quintile: adjusted HR 0.41; 95%CI (0.220.76) p for trend &lt;0.001 for FRAP; adjusted HR 0.52; 95%CI (0.280.97) p for trend &lt;0.001 for TRAP) but not in nonsmokers. In former smokers, the association with FRAP intake was statistically significant (highest vs. lowest quintile: adjusted HR 0.4; 95%CI (0.210.75) p &lt; 0.05); no association was observed for TRAP. Dietary antioxidant capacity intake from different sources of plant foods is associated with a reduction in the risk of GC