Predicted basal metabolic rate and cancer risk in the European Prospective Investigation into Cancer and Nutrition.

Emerging evidence suggests that a metabolic profile associated with obesity may be a more relevant risk factor for some cancers than adiposity per se. Basal metabolic rate (BMR) is an indicator of overall body metabolism and may be a proxy for the impact of a specific metabolic profile on cancer risk. Therefore, we investigated the association of predicted BMR with incidence of 13 obesity-related cancers in the European Prospective Investigation into Cancer and Nutrition (EPIC). BMR at baseline was calculated using the WHO/FAO/UNU equations and the relationships between BMR and cancer risk were investigated using multivariable Cox proportional hazards regression models. A total of 141,295 men and 317,613 women, with a mean follow-up of 14 years were included in the analysis. Overall, higher BMR was associated with a greater risk for most cancers that have been linked with obesity. However, among normal weight participants, higher BMR was associated with elevated risks of esophageal adenocarcinoma (hazard ratio per 1-standard deviation change in BMR [HR1-SD ]: 2.46; 95% CI 1.20; 5.03) and distal colon cancer (HR1-SD : 1.33; 95% CI 1.001; 1.77) among men and with proximal colon (HR1-SD : 1.16; 95% CI 1.01; 1.35), pancreatic (HR1-SD : 1.37; 95% CI 1.13; 1.66), thyroid (HR1-SD : 1.65; 95% CI 1.33; 2.05), postmenopausal breast (HR1-SD : 1.17; 95% CI 1.11; 1.22) and endometrial (HR1-SD : 1.20; 95% CI 1.03; 1.40) cancers in women. These results indicate that higher BMR may be an indicator of a metabolic phenotype associated with risk of certain cancer types, and may be a useful predictor of cancer risk independent of body fatness.

Dairy Products and Cancer Risk in a Northern Sweden Population.

The role of dairy products in cancer is unclear. We assessed consumption of fermented milk, non-fermented milk, cheese, and butter, estimated from semi-quantitative food frequency questionnaires, in relation to prospective risk of breast, prostate, colorectal, smoking-, and obesity-related cancers in 101,235 subjects, including 12,552 cancer cases, in the population-based Northern Sweden Health and Disease Study. Most analyses (n = 20) rendered null results. In men, we observed an increased prostate cancer risk among high-consumers of cheese (hazard ratio (HR) for highest vs. lowest quintile (Q5-Q1), 1.11; 95% CI, 0.97-1.27; Ptrend = 0.013). In women, high-consumers of cheese had a decreased risk of overall cancer (HR Q5-Q1, 0.95; 95% CI, 0.88-1.04; Ptrend = 0.039), smoking-related (HR Q5-Q1, 0.84; 95% CI, 0.72-0.97; Ptrend ≤ 0.001), and colorectal cancers (HR Q5-Q1, 0.82; 95% CI, 0.63-1.07; Ptrend = 0.048). Butter yielded a weak decreased obesity-related cancer risk in women (HR Q5-Q1, 0.91; 95% CI, 0.81-1.02; Ptrend = 0.049). Fermented milk yielded HRs below zero in women, but with no clear linear associations. In conclusion, this study does not support any major adverse or beneficial effects of fermented milk, non-fermented milk, cheese, and butter in the diet from a cancer risk perspective.

Tea and coffee consumption in relation to DNA methylation in four European cohorts.

Lifestyle factors, such as food choices and exposure to chemicals, can alter DNA methylation and lead to changes in gene activity. Two such exposures with pharmacologically active components are coffee and tea consumption. Both coffee and tea have been suggested to play an important role in modulating disease-risk in humans by suppressing tumour progression, decreasing inflammation and influencing estrogen metabolism. These mechanisms may be mediated by changes in DNA methylation. To investigate if DNA methylation in blood is associated with coffee and tea consumption, we performed a genome-wide DNA methylation study for coffee and tea consumption in four European cohorts (N = 3,096). DNA methylation was measured from whole blood at 421,695 CpG sites distributed throughout the genome and analysed in men and women both separately and together in each cohort. Meta-analyses of the results and additional regional-level analyses were performed. After adjusting for multiple testing, the meta-analysis revealed that two individual CpG-sites, mapping to DNAJC16 and TTC17, were differentially methylated in relation to tea consumption in women. No individual sites were associated with men or with the sex-combined analysis for tea or coffee. The regional analysis revealed that 28 regions were differentially methylated in relation to tea consumption in women. These regions contained genes known to interact with estradiol metabolism and cancer. No significant regions were found in the sex-combined and male-only analysis for either tea or coffee consumption.

Pre-diagnostic concordance with the WCRF/AICR guidelines and survival in European colorectal cancer patients: a cohort study.

BACKGROUND: Cancer survivors are advised to follow lifestyle recommendations on diet, physical activity, and body fatness proposed by the World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) for cancer prevention. Previous studies have demonstrated that higher concordance with these recommendations measured using an index score (the WCRF/AICR score) was associated with lower cancer incidence and mortality. The aim of this study was to evaluate the association between pre-diagnostic concordance with WCRF/AICR recommendations and mortality in colorectal cancer (CRC) patients. METHODS: The association between the WCRF/AICR score (score range 0-6 in men and 0-7 in women; higher scores indicate greater concordance) assessed on average 6.4 years before diagnosis and CRC-specific (n = 872) and overall mortality (n = 1,113) was prospectively examined among 3,292 participants diagnosed with CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (mean follow-up time after diagnosis 4.2 years). Multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality. RESULTS: The HRs (95% CIs) for CRC-specific mortality among participants in the second (score range in men/women: 2.25-2.75/3.25-3.75), third (3-3.75/4-4.75), and fourth (4-6/5-7) categories of the score were 0.87 (0.72-1.06), 0.74 (0.61-0.90), and 0.70 (0.56-0.89), respectively (P for trend <0.0001), compared to participants with the lowest concordance with the recommendations (category 1 of the score: 0-2/0-3). Similar HRs for overall mortality were observed (P for trend 0.004). Meeting the recommendations on body fatness and plant food consumption were associated with improved survival among CRC cases in mutually adjusted models. CONCLUSIONS: Greater concordance with the WCRF/AICR recommendations on diet, physical activity, and body fatness prior to CRC diagnosis is associated with improved survival among CRC patients.

Whole-grain products and whole-grain types are associated with lower all-cause and cause-specific mortality in the Scandinavian HELGA cohort.

No study has yet investigated the intake of different types of whole grain (WG) in relation to all-cause and cause-specific mortality in a healthy population. The aim of the present study was to investigate the intake of WG products and WG types in relation to all-cause and cause-specific mortality in a large Scandinavian HELGA cohort that, in 1992-8, included 120 010 cohort members aged 30-64 years from the Norwegian Women and Cancer Study, the Northern Sweden Health and Disease Study, and the Danish Diet Cancer and Health Study. Participants filled in a FFQ from which data on the intake of WG products were extracted. The estimation of daily intake of WG cereal types was based on country-specific products and recipes. Mortality rate ratios (MRR) and 95 % CI were estimated using the Cox proportional hazards model. A total of 3658 women and 4181 men died during the follow-up (end of follow-up was 15 April 2008 in the Danish sub-cohort, 15 December 2009 in the Norwegian sub-cohort and 15 February 2009 in the Swedish sub-cohort). In the analyses of continuous WG variables, we found lower all-cause mortality with higher intake of total WG products (women: MRR 0·89 (95 % CI 0·86, 0·91); men: MRR 0·89 (95 % CI 0·86, 0·91) for a doubling of intake). In particular, intake of breakfast cereals and non-white bread was associated with lower mortality. We also found lower all-cause mortality with total intake of different WG types (women: MRR 0·88 (95 % CI 0·86, 0·92); men: MRR 0·88 (95 % CI 0·86, 0·91) for a doubling of intake). In particular, WG oat, rye and wheat were associated with lower mortality. The associations were found in both women and men and for different causes of deaths. In the analyses of quartiles of WG intake in relation to all-cause mortality, we found lower mortality in the highest quartile compared with the lowest for breakfast cereals, non-white bread, total WG products, oat, rye (only men), wheat and total WG types. The MRR for highest v. lowest quartile of intake of total WG products was 0·68 (95 % CI 0·62, 0·75, P trend over quartiles< 0·0001) for women and 0·75 (95 % CI 0·68, 0·81, P trend over quartiles< 0·0001) for men. The MRR for highest v. lowest quartile of intake of total WG types was 0·74 (95 % CI 0·67, 0·81, P trend over quartiles< 0·0001) for women and 0·75 (95 % CI 0·68, 0·82, P trend over quartiles< 0·0001) for men. Despite lower statistical power, the analyses of cause-specific mortality according to quartiles of WG intake supported these results. In conclusion, higher intake of WG products and WG types was associated with lower mortality among participants in the HELGA cohort. The study indicates that intake of WG is an important aspect of diet in preventing early death in Scandinavia.

Dietary patterns and whole grain cereals in the Scandinavian countries--differences and similarities. The HELGA project.

OBJECTIVE: To identify dietary patterns with whole grains as a main focus to see if there is a similar whole grain pattern in the three Scandinavian countries; Denmark, Sweden and Norway. Another objective is to see if items suggested for a Nordic Food Index will form a typical Nordic pattern when using factor analysis. SETTING: The HELGA study population is based on samples of existing cohorts: the Norwegian Women and Cancer Study, the Swedish Västerbotten cohort and the Danish Diet, Cancer and Health study. The HELGA study aims to generate knowledge about the health effects of whole grain foods. SUBJECTS: The study included a total of 119 913 participants. DESIGN: The associations among food variables from FFQ were investigated by principal component analysis. Only food groups common for all three cohorts were included. High factor loading of a food item shows high correlation of the item to the specific diet pattern. RESULTS: The main whole grain for Denmark and Sweden was rye, while Norway had highest consumption of wheat. Three similar patterns were found: a cereal pattern, a meat pattern and a bread pattern. However, even if the patterns look similar, the food items belonging to the patterns differ between countries. CONCLUSIONS: High loadings on breakfast cereals and whole grain oat were common in the cereal patterns for all three countries. Thus, the cereal pattern may be considered a common Scandinavian whole grain pattern. Food items belonging to a Nordic Food Index were distributed between different patterns.

Coffee and tea consumption, genotype-based CYP1A2 and NAT2 activity and colorectal cancer risk-results from the EPIC cohort study.

Coffee and tea contain numerous antimutagenic and antioxidant components and high levels of caffeine that may protect against colorectal cancer (CRC). We investigated the association between coffee and tea consumption and CRC risk and studied potential effect modification by CYP1A2 and NAT2 genotypes, enzymes involved in the metabolization of caffeine. Data from 477,071 participants (70.2% female) of the European Investigation into Cancer and Nutrition (EPIC) cohort study were analyzed. At baseline (1992-2000) habitual (total, caffeinated and decaffeinated) coffee and tea consumption was assessed with dietary questionnaires. Cox proportional hazards models were used to estimate adjusted hazard ratio's (HR) and 95% confidence intervals (95% CI). Potential effect modification by genotype-based CYP1A2 and NAT2 activity was studied in a nested case-control set of 1,252 cases and 2,175 controls. After a median follow-up of 11.6 years, 4,234 participants developed CRC (mean age 64.7 ± 8.3 years). Total coffee consumption (high vs. non/low) was not associated with CRC risk (HR 1.06, 95% CI 0.95-1.18) or subsite cancers, and no significant associations were found for caffeinated (HR 1.10, 95% CI 0.97-1.26) and decaffeinated coffee (HR 0.96, 95% CI 0.84-1.11) and tea (HR 0.97, 95% CI 0.86-1.09). High coffee and tea consuming subjects with slow CYP1A2 or NAT2 activity had a similar CRC risk compared to non/low coffee and tea consuming subjects with a fast CYP1A2 or NAT2 activity, which suggests that caffeine metabolism does not affect the link between coffee and tea consumption and CRC risk. This study shows that coffee and tea consumption is not likely to be associated with overall CRC.

Self-reported whole-grain intake and plasma alkylresorcinol concentrations in combination in relation to the incidence of colorectal cancer.

Self-reported food frequency questionnaires (FFQs) have occasionally been used to investigate the association between whole-grain intake and the incidence of colorectal cancer, but the results from those studies have been inconsistent. We investigated this association using intakes of whole grains and whole-grain products measured via FFQs and plasma alkylresorcinol concentrations, a biomarker of whole-grain wheat and rye intake, both separately and in combination (Howe's score with ranks). We conducted a nested case-control study in a cohort from a research project on Nordic health and whole-grain consumption (HELGA, 1992-1998). Incidence rate ratios and 95% confidence intervals were calculated using conditional logistic regression. Plasma alkylresorcinol concentrations alone and Howe's score with ranks were inversely associated with the incidence of distal colon cancer when the highest quartile was compared with the lowest (for alkylresorcinol concentrations, incidence rate ratio = 0.34, 95% confidence interval: 0.13, 0.92; for Howe's score with ranks, incidence rate ratio = 0.35, 95% confidence interval: 0.15, 0.86). No association was observed between whole-grain intake and any colorectal cancer (colon, proximal, distal or rectum cancer) when using an FFQ as the measure/exposure variable for whole-grain intake. The results suggest that assessing whole-grain intake using a combination of FFQs and biomarkers slightly increases the precision in estimating the risk of colon or rectal cancer by reducing the impact of misclassification, thereby increasing the statistical power of the study.

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.

Intake of whole grains from different cereal and food sources and incidence of colorectal cancer in the Scandinavian HELGA cohort.

PURPOSE: A high intake of whole grains has been associated with a lower incidence of colorectal cancer, but few studies are available on the association with whole grains from different cereals, for example, wheat, rye and oats, and none has addressed these separately. The objective of this study was to investigate the association between whole-grain intake and colorectal cancer. METHOD: We used data from the large population-based Scandinavian cohort HELGA consisting of 108,000 Danish, Swedish, and Norwegian persons, of whom 1,123 developed colorectal cancer during a median of 11 years of follow-up. Detailed information on daily intake of whole-grain products, including whole-grain bread, crispbread, and breakfast cereals, was available, and intakes of total whole grains and specific whole-grain species (wheat, rye, and oats) were estimated. Associations between these whole-grain variables and the incidence of colorectal cancer were investigated using Cox proportional hazards models. Intake of whole-grain products was associated with a lower incidence of colorectal cancer per 50-g increment (incidence rate ratio [IRR], 0.94; 95% confidence interval [CI], 0.89, 0.99), and the same tendency was found for total whole-grain intake (IRR pr. 25-g increment, 0.94; 95% CI, 0.88, 1.01). Intake of whole-grain wheat was associated with a lower incidence of colorectal cancer (IRR for highest versus lowest quartile of intake, 0.66; 95% CI, 0.51, 0.85), but no statistical significant linear trend was observed (p for trend: 0.18). No significant association was found for whole-grain rye or oats. CONCLUSION: Whole-grain intake was associated with a lower incidence of colorectal cancer.

Respiration signals from photoplethysmography.

Pulse oximetry is based on the technique of photoplethysmography (PPG) wherein light transmitted through tissues is modulated by the pulse. In addition to variations in light modulation by the cardiac cycle, the PPG signal contains a respiratory modulation and variations associated with changing tissue blood volume of other origins. Cardiovascular, respiratory, and neural fluctuations in the PPG signal are of different frequencies and can all be characterized according to their sinusoidal components. PPG was described in 1937 to measure blood volume changes. The technique is today increasingly used, in part because of developments in semiconductor technology during recent decades that have resulted in considerable advances in PPG probe design. Artificial neural networks help to detect complex nonlinear relationships and are extensively used in electronic signal analysis, including PPG. Patient and/or probe-tissue movement artifacts are sources of signal interference. Physiologic variations such as vasoconstriction, a deep gasp, or yawn also affect the signal. Monitoring respiratory rates from PPG are often based on respiratory-induced intensity variations (RIIVs) contained in the baseline of the PPG signal. Qualitative RIIV signals may be used for monitoring purposes regardless of age, gender, anesthesia, and mode of ventilation. Detection of breaths in adult volunteers had a maximal error of 8%, and in infants the rates of overdetected and missed breaths using PPG were 1.5% and 2.7%, respectively. During central apnea, the rhythmic RIIV signals caused by variations in intrathoracic pressure disappear. PPG has been evaluated for detecting airway obstruction with a sensitivity of 75% and a specificity of 85%. The RIIV and the pulse synchronous PPG waveform are sensitive for detecting hypovolemia. The respiratory synchronous variation of the PPG pulse amplitude is an accurate predictor of fluid responsiveness. Pleth variability index is a continuous measure of the respiratory modulation of the pulse oximeter waveform and has been shown to predict fluid responsiveness in mechanically ventilated patients including infants. The pleth variability index value depends on the size of the tidal volume and on positive end-expiratory pressure. In conclusion, the respiration modulation of the PPG signal can be used to monitor respiratory rate. It is probable that improvements in neural network technology will increase sensitivity and specificity for detecting both central and obstructive apnea. The size of the PPG respiration variation can predict fluid responsiveness in mechanically ventilated patients.

The effect of positive end-expiratory pressure and tripled tidal volume on pleth variability index during hypovolaemia in conscious subjects: a volunteer study.

BACKGROUND: The pulse oximeter measurement pleth variability index (PVI) can detect hypovolaemia during positive pressure ventilation. OBJECTIVES: We studied whether PVI can detect a hypovolaemic state in spontaneously breathing humans and whether better discrimination is obtained by modifying the breathing patterns. DESIGN: Experimental study. SETTING: Clinical physiology department in a university hospital. PARTICIPANTS: Fourteen healthy volunteers aged between 18 and 27 (mean 21) years. INTERVENTIONS: A hypovolaemic state was induced by lower body negative pressure (LBNP) of 40 mmHg (LBNP40) and 15 mmHg (LBNP15). Data were collected in four separate series with normal breathing and application of positive end-expiratory pressure (PEEP) 5 cmH2O, with and without tripling of the tidal volume. MAIN OUTCOME MEASURES: PVI (mean ± standard deviation), heart rate, arterial blood pressure and cardiac index (CI). RESULTS: Cardiac index decreased from 2.4 to 1.7 and 2.1 l min(-1) m(-2) at LBNP40 and LBNP15, respectively (P<0.001). The mean PVI for the four breathing modes increased with the degree of LBNP, from 23.5 ± 5.9% at baseline to 27.9 ± 9.3% at LBNP40, and to 25.2 ± 6.9% at LBNP15 (P<0.01). The greatest increase in PVI, to 31.7 ± 12.3%, was recorded for the PEEP and tripled tidal volume breathing mode when hypovolaemia was induced by LBNP40. However, there was considerable overlap between the LBNP levels. CONCLUSION: The PVI increased significantly for higher LBNP, but overlap was common regardless of breathing mode. The PVI can be used to indicate a hypovolaemic state during spontaneous breathing in groups but not in individuals. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01456559.

Dairy Product Intake and Cardiometabolic Diseases in Northern Sweden: A 33-Year Prospective Cohort Study.

Dairy products are important constituents of most diets, and their association with adverse health outcomes remains a focus. We characterized dairy food intake and examined associations with the incidence of type 2 diabetes (T2D), myocardial infarction (MI) or stroke among 108,065 Swedish men and women. Hazard ratios (HRs) and 95% CIs were estimated using the multivariable Cox proportional hazards models in a population characterized by high milk tolerance. During a mean follow-up of 14.2 years, 11,641 first-time events occurred. Non-fermented milk intake decreased, whereas butter intake increased over the period. For high intake of non-fermented milk, the HR (95% CI) for developing T2D and MI was 1.17 (1.03, 1.34) and 1.23 (1.10, 1.37), respectively, in men. A greater intake of butter, fermented milk, and cheese tended to be associated with a reduced risk of T2D and/or MI. Non-consumers and those who chose low-fat variants of the targeted dairy products had increased risk for T2D, MI, or stroke compared to those in the non-case group. Generally, effect-sizes were small. This prospective study found that non-fermented milk was associated with an increased risk for developing T2D and MI and that subjects abstaining from dairy products or choosing low-fat variants were at greater risk. However, the overall cardiometabolic risk of non-fermented milk intake was judged as low, since the effect sizes were small.

Inflammatory potential of the diet and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

Background: Chronic inflammation plays a critical role in the pathogenesis of the 2 major types of gastric cancer. Several foods, nutrients, and nonnutrient food components seem to be involved in the regulation of chronic inflammation. Objective: We assessed the association between the inflammatory potential of the diet and the risk of gastric carcinoma, overall and for the 2 major subsites: cardia cancers and noncardia cancers. Design: A total of 476,160 subjects (30% men, 70% women) from the European Investigation into Cancer and Nutrition (EPIC) study were followed for 14 y, during which 913 incident cases of gastric carcinoma were identified, including 236 located in the cardia, 341 in the distal part of the stomach (noncardia), and 336 with overlapping or unknown tumor site. The dietary inflammatory potential was assessed by means of an inflammatory score of the diet (ISD), calculated with the use of 28 dietary components and their corresponding inflammatory scores. The association between the ISD and gastric cancer risk was estimated by HRs and 95% CIs calculated by multivariate Cox regression models adjusted for confounders. Results: The inflammatory potential of the diet was associated with an increased risk of gastric cancer. The HR (95% CI) for each increase in 1 SD of the ISD were 1.25 (1.12, 1.39) for all gastric cancers, 1.30 (1.06, 1.59) for cardia cancers, and 1.07 (0.89, 1.28) for noncardia cancers. The corresponding values for the highest compared with the lowest quartiles of the ISD were 1.66 (1.26, 2.20), 1.94 (1.14, 3.30), and 1.07 (0.70, 1.70), respectively. Conclusions: Our results suggest that low-grade chronic inflammation induced by the diet may be associated with gastric cancer risk. This pattern seems to be more consistent for gastric carcinomas located in the cardia than for those located in the distal stomach. This study is listed on the ISRCTN registry as ISRCTN12136108.

Nonfermented milk and other dairy products: associations with all-cause mortality.

Background: A positive association between nonfermented milk intake and increased all-cause mortality was recently reported, but overall, the association between dairy intake and mortality is inconclusive.Objective: We studied associations between intake of dairy products and all-cause mortality with an emphasis on nonfermented milk and fat content.Design: A total of 103,256 adult participants (women: 51.0%) from Northern Sweden were included (7121 deaths; mean follow-up: 13.7 y). Associations between all-cause mortality and reported intakes of nonfermented milk (total or by fat content), fermented milk, cheese, and butter were tested with the use of Cox proportional hazards models that were adjusted for age, sex, body mass index, smoking status, education, energy intake, examination year, and physical activity. To circumvent confounding, Mendelian randomization was applied in a subsample via the lactase LCT-13910 C/T single nucleotide polymorphism that is associated with lactose tolerance and milk intake.Results: High consumers of nonfermented milk (≥2.5 times/d) had a 32% increased hazard (HR: 1.32; 95% CI: 1.18, 1.48) for all-cause mortality compared with that of subjects who consumed milk ≤1 time/wk. The corresponding value for butter was 11% (HR: 1.11; 95% CI: 1.07, 1.21). All nonfermented milk-fat types were independently associated with increased HRs, but compared with full-fat milk, HRs were lower in consumers of medium- and low-fat milk. Fermented milk intake (HR: 0.90; 95% CI: 0.86, 0.94) and cheese intake (HR: 0.93; 95% CI: 0.91, 0.96) were negatively associated with mortality. Results were slightly attenuated by lifestyle adjustments but were robust in sensitivity analyses. Mortality was not significantly associated with the LCT-13910 C/T genotype in the smaller subsample. The amount and type of milk intake was associated with lifestyle variables.Conclusions: In the present Swedish cohort study, intakes of nonfermented milk and butter are associated with higher all-cause mortality, and fermented milk and cheese intakes are associated with lower all-cause mortality. Residual confounding by lifestyle cannot be excluded, and Mendelian randomization needs to be examined in a larger sample.

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.

Prediagnostic intake of dairy products and dietary calcium and colorectal cancer survival--results from the EPIC cohort study.

BACKGROUND: We investigated whether prediagnostic reported intake of dairy products and dietary calcium is associated with colorectal cancer survival. METHODS: Data from 3,859 subjects with colorectal cancer (42.1% male; mean age at diagnosis, 64.2 ± 8.1 years) in the European Investigation into Cancer and Nutrition cohort were analyzed. Intake of dairy products and dietary calcium was assessed at baseline (1992-2000) using validated, country-specific dietary questionnaires. Multivariable Cox regression models were used to calculate HR and corresponding 95% confidence intervals (CI) for colorectal cancer-specific death (n = 1,028) and all-cause death (n = 1,525) for different quartiles of intake. RESULTS: The consumption of total dairy products was not statistically significantly associated with risk of colorectal cancer-specific death (adjusted HR Q4 vs. Q1, 1.17; 95% CI, 0.97-1.43) nor that of all-cause death (Q4 vs. Q1, 1.16; 95% CI, 0.98-1.36). Multivariable-adjusted HRs for colorectal cancer-specific death (Q4 vs. Q1) were 1.21 (95% CI, 0.99-1.48) for milk, 1.09 (95% CI, 0.88-1.34) for yoghurt, and 0.93 (95% CI, 0.76-1.14) for cheese. The intake of dietary calcium was not associated with the risk of colorectal cancer-specific death (adjusted HR Q4 vs. Q1, 1.01; 95% CI, 0.81-1.26) nor that of all-cause death (Q4 vs. Q1, 1.01; 95% CI, 0.84-1.21). CONCLUSIONS: The prediagnostic reported intake of dairy products and dietary calcium is not associated with disease-specific or all-cause risk of death in patients diagnosed with colorectal cancer. IMPACT: The impact of diet on cancer survival is largely unknown. This study shows that despite its inverse association with colorectal cancer risk, the prediagnostic intake of dairy and dietary calcium does not affect colorectal cancer survival.

Food and water security issues in Russia II: water security in general population of Russian Arctic, Siberia and Far East, 2000-2011.

BACKGROUND: Poor state of water supply systems, shortage of water purification facilities and disinfection systems, low quality of drinking water generally in Russia and particularly in the regions of the Russian Arctic, Siberia and Far East have been defined in the literature. However, no standard protocol of water security assessment has been used in the majority of studies. STUDY DESIGN AND METHODS: Uniform water security indicators collected from Russian official statistical sources for the period 2000-2011 were used for comparison for 18 selected regions in the Russian Arctic, Siberia and Far East. The following indicators of water security were analyzed: water consumption, chemical and biological contamination of water reservoirs of Categories I and II of water sources (centralized--underground and surface, and non-centralized) and of drinking water. RESULTS: Water consumption in selected regions fluctuated from 125 to 340 L/person/day. Centralized water sources (both underground and surface sources) are highly contaminated by chemicals (up to 40-80%) and biological agents (up to 55% in some regions), mainly due to surface water sources. Underground water sources show relatively low levels of biological contamination, while chemical contamination is high due to additional water contamination during water treatment and transportation in pipelines. Non-centralized water sources are highly contaminated (both chemically and biologically) in 32-90% of samples analyzed. Very high levels of chemical contamination of drinking water (up to 51%) were detected in many regions, mainly in the north-western part of the Russian Arctic. Biological contamination of drinking water was generally much lower (2.5-12%) everywhere except Evenki AO (27%), and general and thermotolerant coliform bacteria predominated in drinking water samples from all regions (up to 17.5 and 12.5%, correspondingly). The presence of other agents was much lower: Coliphages--0.2-2.7%, Clostridia spores, Giardia cysts, pathogenic bacteria, Rotavirus--up to 0.8%. Of a total of 56 chemical pollutants analyzed in water samples from centralized water supply systems, 32 pollutants were found to be in excess of hygienic limits, with the predominant pollutants being Fe (up to 55%), Cl (up to 57%), Al (up to 43%) and Mn (up to 45%). CONCLUSION: In 18 selected regions of the Russian Arctic, Siberia and Far East Category I and II water reservoirs, water sources (centralized--underground, surface; non-centralized) and drinking water are highly contaminated by chemical and biological agents. Full-scale reform of the Russian water industry and water security system is urgently needed, especially in selected regions.

Coffee and tea intake and risk of brain tumors in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study.

BACKGROUND: In a recent US cohort study, total coffee and tea consumption was inversely associated with risk of glioma, and experimental studies showed that caffeine can slow the invasive growth of glioblastoma. OBJECTIVE: The objective was to examine the relation between coffee and tea intake and the risk of glioma and meningioma in a large European cohort study, the European Prospective Investigation into Cancer and Nutrition (EPIC). DESIGN: Data on coffee and tea intake were collected from men and women recruited into the EPIC cohort study. Over an average of 8.5 y of follow-up, 343 cases of glioma and 245 cases of meningioma were newly diagnosed in 9 countries. We used Cox proportional hazards models to examine the relation between coffee and tea and brain tumors. RESULTS: We observed no associations between coffee, tea, or combined coffee and tea consumption and risk of either type of brain tumor when using quantiles based on country-specific distributions of intake. However, a significant inverse association was observed for glioma risk among those consuming ≥100 mL coffee and tea per day compared with those consuming <100 mL/d (hazard ratio: 0.66; 95% CI: 0.44, 0.97; P = 0.03). The association was slightly stronger in men (hazard ratio: 0.59; 95% CI: 0.34, 1.01) than in women (hazard ratio: 0.74; 95% CI: 0.42, 1.31), although neither was statistically significant. CONCLUSIONS: In this large cohort study, we observed an inverse association between total coffee and tea consumption and risk of glioma that was consistent with the findings of a recent study. These findings, if further replicated in other studies, may provide new avenues of research on gliomas.