Association of the habitual dietary intake with the fatty liver index and effect modification by metabotypes in the population-based KORA-Fit study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is an emerging threat for public health with diet being a major risk factor in disease development and progression. However, the effects of habitual food consumption on fatty liver are still inconclusive as well as the proposed role of the individuals' metabolic profiles. Therefore, the aim of our study is to examine the associations between diet and NAFLD with an emphasis on the influence of specific metabotypes in the general population. METHODS: A total of 689 participants (304 men and 385 women) of the KORA-Fit (S4) survey, a follow-up study of the population-based KORA cohort study running in the Region of Augsburg, Germany, were included in this analysis. Dietary information was derived from repeated 24-h food lists and a food frequency questionnaire. The intake of energy and energy-providing nutrients were calculated using the national food composition database. The presence of fatty liver was quantified by the fatty liver index (FLI), and metabotypes were calculated using K-means clustering. Multivariable linear regression models were used for the analysis of habitual food groups and FLI; for the evaluation of macronutrients, energy substitution models were applied. RESULTS: A higher consumption of nuts and whole grains, and a better diet quality (according to Alternate Healthy Eating Index and Mediterranean Diet Score) were associated with lower FLI values, while the intake of soft drinks, meat, fish and eggs were associated with a higher FLI. The isocaloric substitution of carbohydrates with polyunsaturated fatty acids was associated with a decreased FLI, while substitution with monounsaturated fatty acids and protein showed increased FLI. Statistically significant interactions with the metabotype were observed for most food groups. CONCLUSION: The consumption of plant-based food groups, including nuts and whole grains, and diet quality, were associated with lower FLI values, whereas the intake of soft drinks and products of animal origin (meat, fish, eggs) were associated with a higher FLI. The observed statistically significant interactions with the metabotype for most food groups could help to develop targeted prevention strategies on a population-based level if confirmed in independent prospective studies.

Associations between anthropometric parameters and immune-phenotypical characteristics of circulating Tregs and serum cytokines.

OBJECTIVE: To investigate the associations between several anthropometric parameters and regulatory T cells (Tregs) and circulating cytokines in a population-based cohort. METHODS: Between 2018 and 2021, a total of 238 participants were examined up to three times within the scope of the MEGA study in Augsburg, Germany. Tregs were analyzed using flow cytometry and the serum concentrations of 52 cytokines were determined. Anthropometric parameters were measured, using also bioelectrical impedance analysis: body mass index (BMI), relative total body fat, relative visceral adipose tissue (rVAT), waist circumference (WC), waist-to-hip ratio (WHR) and body fat distribution. Associations were analyzed using linear mixed models with random intercept (Tregs) and conventional linear regression models (cytokines). RESULTS: WC and WHR were inversely associated with the general Treg subset. Four parameters (BMI, rVAT, WC, and WHR) were inversely associated with the conventional Treg population. Three cytokines showed a particularly strong association with several anthropometric parameters: the cutaneous T-cell attracting chemokine was inversely associated with anthropometric parameters, while hepatocyte growth factor and interleukine-18 showed positive associations. CONCLUSIONS: Anthropometric measures are associated with Tregs and serum cytokine concentrations revealing new important interconnections between obesity and the adaptive immune system.

Sex-specific associations between systolic, diastolic and pulse pressure and hemostatic parameters in the population-based KORA-Fit study: a cross-sectional study.

BACKGROUND: Several prior studies postulated an effect of hypertension on coagulation factors. However, population-based studies investigating the sex-specific associations between hypertension and hemostatic parameters are scarce. Therefore, we investigated the relationship between blood pressure and parameters of coagulation, namely activated partial thromboplastin time (aPTT), international normalized ratio (INR), fibrinogen, factor VIII, antithrombin III, protein C, protein S, and D-dimer in men and women from the general population. METHODS: Based on 803 participants (376 men, 427 women) from the KORA-Fit Study the sex-specific relationship between systolic, diastolic, and pulse pressure and commonly measured coagulation factors were investigated using multivariable-adjusted linear regression models. RESULTS: Hypertensive males had significantly higher median fibrinogen levels and factor VIII activity in comparison to normotensive males. There was a statistically significant difference between females with and without hypertension regarding the parameter fibrinogen, D-dimers, Protein S activity, and factor VIII activity. In multivariable linear regression analyses no significant association between systolic blood pressure, diastolic blood pressure, as well as pulse pressure and the investigated hemostatic parameters was found in men. In women, a significant positive association could be observed between systolic blood pressure and D-dimer level [ß-estimate per mmHg increase 3.37 (95% CI 0.935-5.804; p = 0.007)] and between pulse pressure and D-dimer level [ß-estimate per mmHg increase 5.351 (95% CI 1.772-8.930; p = 0.003)]. CONCLUSIONS: It appears that sex differences exist in the association between blood pressure parameters and commonly measured coagulation markers in the general population. Further studies are needed to identify the underlying causes.

COVID-19 risk perceptions, worries and preventive behaviors in patients with previous myocardial infarction: results from the myocardial infarction registry Augsburg.

Despite the known association of chronic cardiovascular diseases and more severe courses of COVID-19, little is known about individual risk perception of patients with a history of acute myocardial infarction (AMI) and resulting preventive behaviours. In May 2020, a postal survey was conducted, including 150 patients with previous AMI from the myocardial infarction registry Augsburg. The study objective was to assess COVID-19 knowledge, individual risk perception, worries, infection likelihood and preventive behaviours in this patient cohort. From the 100 respondents, 69.7% perceived themselves to be at high risk of developing a severe course of COVID-19. There was a significant positive correlation between dangerousness assessment and knowledge on COVID-19. Despite a majority (70%) of patients rating their susceptibility for an infection as moderate to very high, the individual likelihood of being infected was rated at only 3%. Almost 70% of patients with previous MI classified themselves at high risk for a severe course of COVID-19 infection. As seen in other risk groups as well, the availability of valuable information sources as well as the support in individual risk reduction strategies and psychological coping mechanisms are mandatory, especially since higher knowledge correlates with dangerousness assessment and might lead to better compliance with preventive behaviours.

Inflammatory plasma proteins predict short-term mortality in patients with an acute myocardial infarction.

BACKGROUND: The aim of this study was to investigate the association between inflammatory markers and 28-day mortality in patients with ST-elevation myocardial infarction (STEMI). METHODS: In 398 STEMI patients recorded between 2009 and 2013 by the population-based Myocardial Infarction Registry Augsburg, 92 protein biomarkers were measured in admission arterial blood samples using the OLINK inflammatory panel. In multivariable-adjusted logistic regression models, the association between each marker and 28-day mortality was investigated. The values of the biomarkers most significantly associated with mortality were standardized and summarized to obtain a prediction score for 28-day mortality. The predictive ability of this biomarker score was compared to the established GRACE score using ROC analysis. Finally, a combined total score was generated by adding the standardized biomarker score to the standardized GRACE score. RESULTS: The markers IL-6, IL-8, IL-10, FGF-21, FGF-23, ST1A1, MCP-1, 4E-BP1, and CST5 were most significantly associated with 28-day mortality, each with FDR-adjusted (false discovery rate adjusted) p-values of < 0.01 in the multivariable logistic regression model. In a ROC analysis, the biomarker score and the GRACE score showed comparable predictive ability for 28-day mortality (biomarker score AUC: 0.7859 [CI: 0.6735-0.89], GRACE score AUC: 0.7961 [CI: 0.6965-0.8802]). By combining the biomarker score and the Grace score, the predictive ability improved with an AUC of 0.8305 [CI: 0.7269-0.9187]. A continuous Net Reclassification Improvement (cNRI) of 0.566 (CI: 0.192-0.94, p-value: 0.003) and an Integrated Discrimination Improvement (IDI) of 0.083 ((CI: 0.016-0.149, p-value: 0.015) confirmed the superiority of the combined score over the GARCE score. CONCLUSIONS: Inflammatory biomarkers may play a significant role in the pathophysiology of acute myocardial infarction (AMI) and AMI-related mortality and might be a promising starting point for personalized medicine, which aims to provide each patient with tailored therapy.

Host traits, lifestyle and environment are associated with human skin bacteria.

BACKGROUND: The human skin offers diverse ecosystems for microbial symbionts. However, the factors shaping skin-microbiome interactions are still insufficiently characterized. This contrasts with the broader knowledge about factors influencing gut microbiota. OBJECTIVES: We aimed to investigate major patterns of association of host traits, lifestyle and environmental factors with skin bacteria in two German populations. METHODS: This is a cross-sectional study with 647 participants from two population-based German cohorts, PopGen (n = 294) and KORA FF4 (n = 353), totalling 1794 skin samples. The V1-V2 regions of the 16S ribosomal RNA (rRNA) gene were sequenced. Associations were tested with two bacterial levels, community (beta diversity) and 16S rRNA gene amplicon sequence variants (ASVs). RESULTS: We validated known associations of the skin microbiota with skin microenvironment, age, body mass index and sex. These factors were associated with beta diversity and abundance of ASVs in PopGen, which was largely replicated in KORA FF4. Most intriguingly, dietary macronutrients and total dietary energy were associated with several ASVs. ASVs were also associated with smoking, alcohol consumption, skin pH, skin type, transepidermal water loss, education and several environmental exposures, including hours spent outdoors. Associated ASVs included members of the genera Propionibacterium, Corynebacterium and Staphylococcus. CONCLUSIONS: We expand the current understanding of factors associated with the skin bacterial community. We show the association of diet with skin bacteria. Finally, we hypothesize that the skin microenvironment and host physiology would shape the skin bacterial community to a greater extent compared with a single skin physiological feature, lifestyle and environmental exposure.

[From the MONICA-project via KORA to the NAKO-study: Practical Utility of Epidemiological Studies in Augsburg Region]. / Vom MONICA-Projekt über KORA zur NAKO-Studie: Vom praktischen Nutzen von Bevölkerungsstudien in der Region Augsburg.

The objective of the WHO-MONICA study was to determine the influence of changing risk factors and treatment options on myocardial infarction rates in populations in a 10-year time period. For this purpose, a population-based myocardial infarction registry was established in 1984 in Augsburg (covering the city of Augsburg and 2 adjacent counties) in order to continuously register all inhabitants of the region who had a myocardial infarction during the study period. In addition, three cross-sectional studies based on random population samples (1984/85, 1989/90 and 1994/95) were carried out. Our data revealed a continuous decrease of myocardial infarction incidence and demonstrated that the decrease of coronary mortality can be ascribed to decreasing myocardial infarction incidence and longer survival after myocardial infarction. Until today the myocardial infarction registry continues to be a permanent part of the Cooperative Health Research in the Region of Augsburg (KORA). Moreover, within the framework of KORA, a fourth population-based cross-sectional study was carried out in 1999/2001. Meanwhile, more than 18 000 study participants have been followed-up for specific endpoints for up to 30 years. A large number of publications, which address cardiovascular diseases, type 2 diabetes mellitus, lung diseases, environmental and genetic questions, health services research and numerous other topics, are based on the KORA study. Today we know that the development of chronic diseases can be ascribed to a complex interaction of social factors, health policy conditions, health behavior, risk factors and molecular mechanisms. To tackle the challenges posed by these multiple factors in Germany, NAKO (Nationale Kohorte), the largest nation-wide long-term study so far, was initiated. Within the framework of the NAKO study, 200 000 persons aged between 20 and 69 years in Germany - thereof 20 000 persons in the region of Augsburg - will be examined and interviewed in the next 10 years, and widespread diseases will be investigated with modern epidemiological methods. The results of these epidemiological long-term studies will contribute to the prevention, early diagnosis and best possible treatment of widespread diseases.

[The design of a nationwide cohort study in Germany : the pretest studies of the German National Cohort (GNC)]. / Das Design der Machbarkeitsstudien für eine bundesweite Kohortenstudie in Deutschland : Die Pretests der Nationalen Kohorte (NAKO).

The German National Cohort (GNC) is the largest population-based cohort study in Germany. Beginning in 2014, a total of 200,000 women and men aged 20-69 years will be examined in 18 study centers. The aim of the study is to investigate the etiology of chronic diseases in relation to lifestyle, genetic, socioeconomic, and environmental factors and to develop appropriate methods for early diagnosis and prevention of diseases such as cardiovascular and respiratory diseases, cancer, diabetes, neurodegenerative/psychiatric diseases, as well as musculoskeletal and infectious diseases. Pretest studies (phase 1 and 2) were conducted to select methods, instruments, and procedures for the main study, to develop standard operating procedures, and to design and test the examination program according to acceptance, expected duration, and feasibility. The pretest studies included testing of interviews, questionnaires, anthropometric measurements, several medical examinations, and the collection of biosamples. In addition, the logistic, technical, and personnel infrastructure for the main study could be established including the study centers, the central infrastructure for data management, processes to coordinate the study, and data protection and quality management concepts. The examination program for the main phase of the GNC was designed and optimized based on the results of the pretest studies. The GNC is a population-based, highly standardized and excellently phenotyped cohort that will be the basis for new strategies for risk assessment and identification, early diagnosis, and prevention of multifactorial diseases.

Feasibility and quality development of biomaterials in the pretest studies of the German National Cohort.

BACKGROUND: The German National Cohort (GNC) is designed to address research questions concerning a wide range of possible causes of major chronic diseases (e.g. cancer, diabetes, infectious, allergic, neurologic and cardiovascular diseases) as well as to identify risk factors and prognostic biomarkers for early diagnosis and prevention of these diseases. The collection of biomaterials in combination with extensive information from questionnaires and medical examinations represents one of the central study components. OBJECTIVES: In two pretest studies of the German National Cohort conducted between 2011 and 2013, a range of biomaterials from a defined number of participants was collected. Ten study centres were involved in pretest 1 and 18 study centres were involved in pretest 2. Standard operation procedures (SOP) were developed and evaluated to minimize pre-analytical artefacts during biosample collection. Within the pretest studies different aspects concerning feasibility of sample collection/preparation [pretest 1 (a)] and quality control of biomarkers and proteome analyses were investigated [pretest 1 (b), (c)]. Additionally, recruitment of study participants for specific projects and examination procedures of all study centres in a defined time period according to common standards as well as transportation and decentralized storage of biological samples were tested (pretest 2). These analyses will serve as the basis for the biomaterial collection in the main study of the GNC starting in 2014. MATERIALS AND METHODS: Participants, randomly chosen from the population (n = 1000 subjects recruited at ten study sites in pretest 1) were asked to donate blood, urine, saliva and stool samples. Additionally, nasal and oropharyngeal swabs were collected at the study sites and nasal swabs were collected by the participants at home. SOPs for sample collection, preparation, storage and transportation were developed and adopted for pretest 2. In pretest 2, 18 study sites (n = 599 subjects) collected biomaterials mostly identical to pretest 1. Biomarker analyses to test the quality of the biomaterials were performed. RESULTS: In pretest 1 and 2, it was feasible to collect all biomaterials from nearly all invited participants without major problems. The mean response rate of the subjects was 95 %. As one important result we found for example that after blood draw the cellular fraction should be separated from the plasma and serum fractions during the first hour with no significant variation for up to 6 h at 4 ℃ for all analysed biomarkers. Moreover, quality control of samples using a proteomics approach showed no significant clustering of proteins according to different storage conditions. All developed SOPs were validated for use in the main study after some adaptation and modification. Additionally, electronic and paper documentation sheets were developed and tested to record time stamps, volumes, freezing times, and aliquot numbers of the collected biomaterials. DISCUSSION: The collection of the biomaterials was feasible without major problems at all participating study sites. However, the processing times were in some cases too long. To avoid pre-analytical artefacts in sample collection, appropriate standardisation among the study sites is necessary. To achieve this, blood and urine collection will have to be adapted to specific conditions of usage of liquid handling robots, which will be available at all participating study centres in the main study of the GNC. Strict compliance with the SOPs, thorough training of the staff and accurate documentation are mandatory to obtain high sample quality for later analyses. The so obtained biomaterials represent a valuable resource for research on infectious and other common complex diseases in the GNC.

Smoking and the risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Smoking is not associated with prostate cancer incidence in most studies, but associations between smoking and fatal prostate cancer have been reported. METHODS: During 1992 and 2000, lifestyle information was assessed via questionnaires and personal interview in a cohort of 145,112 European men. Until 2009, 4623 incident cases of prostate cancer were identified, including 1517 cases of low-grade, 396 cases of high grade, 1516 cases of localised, 808 cases of advanced disease, and 432 fatal cases. Multivariable Cox proportional hazards regression models were used to examine the association of smoking status, smoking intensity, and smoking duration with the risk of incident and fatal prostate cancer. RESULTS: Compared with never smokers, current smokers had a reduced risk of prostate cancer (RR=0.90, 95% CI: 0.83-0.97), which was statistically significant for localised and low-grade disease, but not for advanced or high-grade disease. In contrast, heavy smokers (25+ cigarettes per day) and men who had smoked for a long time (40+ years) had a higher risk of prostate cancer death (RR=1.81, 95% CI: 1.11-2.93; RR=1.38, 95% CI: 1.01-1.87, respectively). CONCLUSION: The observation of an increased prostate cancer mortality among heavy smokers confirms the results of previous prospective studies.

[Development and first results of fast and cost-effective examination methods for an ophthalmological screening within the National Cohort]. / Entwicklung und erste Anwendungserfahrungen einer schnellen und kostengünstigen ophthalmologischen Untersuchung für die Nationale Kohorte.

BACKGROUND: For an implemented ophthalmological screening within a German long-term cohort study (National Cohort) simple and effective methods for an examination of visual acuity and for non-mydriatic retina photografies should be evaluated. Furthermore standard operating-procedures (SOP) should be developed. METHODS: In the years 2011 and 2012 pinhole visual acuity measurements and automated retina photographies (DRS, CenterVue S. p. a., Padua, Italy) were made at three different epidemiological study centers within Germany. Furthermore, anterior segment images were taken by the camera. Standard operating procedures (SOP) regarding the ophthalmological screening were developed and evaluated within the study. The main question was whether it is possible to implement the screening methods within the National Cohort. Further main outcomes were quality and interpretability of the taken images. RESULTS: 457 subjects (914 eyes) were examined within the investigation. Median VA was 0.8 for right and left eyes (p > 0.42). Image quality of the photographies was good in 491 cases (54 %), fair in 239 cases (26 %) and bad in 179 cases (20 %). The usability of the images was without limitations in 686 cases (75 %), limited in 152 cases (17 %) and not given in 71 cases (8 %). Increasing age of the subjects was slightly correlated with decreasing image quality (r = 0.26) and decreasing image usability (r = 0.2). Anterior segment photographies were usable in 176 eyes (56 %). CONCLUSION: The developed screening method fulfilled the specifications of the National Cohort. The used pinhole visual acuity examination was fast and cheap. Image quality and usability of the retina photographies could be improved with prolonged pupil recovery times. The quality of the anterior segment images could not fulfill the expectations and were taken out of the further examinations of the ophthalmological screening. The written SOP showed good acceptance within the investigators' daily routine. The ophthalmological screening within the National Cohort generates information (e. g., pathologies of the vessels or of the retina) which are useful not only from an ophthalmological point of view.

Anterior-wall and non-anterior-wall STEMIs do not differ in long-term mortality: results from the augsburg myocardial infarction registry.

Background: Different ST-segment elevation myocardial infarction (STEMI) localizations go along with dissimilarities in the size of the affected myocardium, the causing coronary vessel occlusion, and the right ventricular participation. Therefore, this study aims to clarify if there is any difference in long-term survival between anterior- and non-anterior-wall STEMI. Methods: This study included 2,195 incident STEMI cases that occurred between 2009 and 2017, recorded by the population-based Augsburg Myocardial Infarction Registry, Germany. The study population comprised 1.570 men and 625 women aged 25-84 years at acute myocardial infarction. The patients were observed from the day of their first acute event with an average follow-up period of 4.3 years, (standard deviation: 3.0). Survival analyses and multivariable Cox regression analyses were performed to examine the association between infarction localizations and long-term all-cause mortality. Results: Of the 2,195 patients, 1,118 had an anterior (AWS)- and 1,077 a non-anterior-wall-STEMI (NAWS). No significant associations of the STEMI localization with long-term mortality were found. When comparing AWS with NAWS, a hazard ratio of 0.91 [95% confidence interval: 0.75-1.10] could be calculated after multivariable adjustment. In contrast to NAWS, AWS was associated with a greater <28 day mortality, less current or former smoking and higher creatine kinase-myocardial band levels (CK-MB) and went along with a higher frequency of impaired left ventricular ejection fraction (<30%). Conclusions: Despite pathophysiological differences between AWS and NAWS, and identified differences in multiple clinical characteristics, no significant differences in long-term mortality between both groups were observed.

[The German National Cohort]. / Die Nationale Kohorte.

The German National Cohort (GNC) is a joint interdisciplinary endeavour of scientists from the Helmholtz Association, universities and other German research institutes. Its aim is to investigate the development of major chronic diseases (cardiovascular diseases, cancer, diabetes, neurodegenerative psychiatric diseases, pulmonary and infectious diseases), the subclinical stages and functional changes. In 18 study centres across Germany, a representative sample of the general population will be drawn to recruit in total 200,000 men and women aged 20-69 years. In addition to interviews and questionnaires, the baseline assessment includes a series of medical examinations and the collection of a diverse range of biomaterials. In 20% of the participants, an intensified assessment programme is foreseen. Also in 40,000 participants, magnetic resonance imaging of the whole body, heart and brain will be performed. After 5 years, a follow-up examination will be performed in all subjects and active follow-up by postal questionnaires is planned every 2-3 years. The GNC will provide an excellent basis for future population-based epidemiology in Germany and results will help identify new and tailored strategies for prevention, prediction and early detection of major diseases.

Prognostic value of stress hyperglycemia ratio on short- and long-term mortality after acute myocardial infarction.

AIMS: Prior studies demonstrated an association between hospital admission blood glucose and mortality in acute myocardial infarction (AMI). Because stress hyperglycemia ratio (SHR) has been suggested as a more reliable marker of stress hyperglycemia this study investigated to what extent SHR in comparison with admission blood glucose is associated with short- and long-term mortality in diabetic and non-diabetic AMI patients. METHODS: The analysis was based on 2,311 AMI patients aged 25-84 years from the population-based Myocardial Infarction Registry Augsburg (median follow-up time 6.5 years [IQR: 4.9-8.1]). The SHR was calculated as admission glucose (mg/dl)/(28.7 × HbA1c (%)-46.7). Using logistic and COX regression analyses the associations between SHR and admission glucose and mortality were investigated. RESULT: Higher admission glucose and higher SHR were significantly and nonlinearly associated with higher 28-day mortality in AMI patients with and without diabetes. In patients without diabetes, the AUC for SHR was significantly lower than for admission glucose (SHR: 0.6912 [95%CI 0.6317-0.7496], admission glucose: 0.716 [95%CI 0.6572-0.7736], p-value: 0.0351). In patients with diabetes the AUCs were similar for SHR and admission glucose. Increasing admission glucose and SHR were significantly nonlinearly associated with higher 5-year all-cause mortality in AMI patients with diabetes but not in non-diabetic patients. AUC values indicated a comparable prediction of 5-year mortality for both measures in diabetic and non-diabetic patients. CONCLUSIONS: Stress hyperglycemia in AMI patients plays a significant role mainly with regard to short-term prognosis, but barely so for long-term prognosis, underlining the assumption that it is a transient dynamic disorder that occurs to varying degrees during the acute event, thereby affecting prognosis.

Estimated enterolignans, lignan-rich foods, and fibre in relation to survival after postmenopausal breast cancer.

BACKGROUND: Lignans - oestrogenic substances present in various foods - are associated with postmenopausal breast cancer risk, but not much is known regarding their effects on survival. METHODS: In a follow-up study of 2653 postmenopausal breast cancer patients diagnosed between 2001 and 2005, vital status and causes of death were verified through end of 2009. Hazard ratios (HRs) and 95% confidence intervals (CIs) for estimated enterolignans, lignan-rich foods, and dietary fibre in relation to overall survival (OS) and breast cancer-specific survival (BCSS) were assessed using Cox proportional hazards models stratified by age at diagnosis and adjusted for prognostic/confounding factors. RESULTS: Median follow-up time was 6.4 years, and 321 women died, 235 with breast cancer. High estimated enterolactone and enterodiol levels were associated with significantly lower overall mortality (highest quintile, HR=0.60, 95% CI=0.40-0.89, P(Trend)=0.02 and HR=0.63, 95% CI=0.42-0.95, P(Trend)=0.02, respectively). Fibre intake was also associated with a significantly lower overall mortality. Differentiated by median fibre intake, associations with estimated enterolignans were still evident at low but not high fibre intake. There was no effect modification by oestrogen receptor status and menopausal hormone therapy. CONCLUSION: Postmenopausal breast cancer patients with high estimated enterolignans may have a better survival.

General and abdominal adiposity and risk of death in Europe.

BACKGROUND: Previous studies have relied predominantly on the body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) to assess the association of adiposity with the risk of death, but few have examined whether the distribution of body fat contributes to the prediction of death. METHODS: We examined the association of BMI, waist circumference, and waist-to-hip ratio with the risk of death among 359,387 participants from nine countries in the European Prospective Investigation into Cancer and Nutrition (EPIC). We used a Cox regression analysis, with age as the time variable, and stratified the models according to study center and age at recruitment, with further adjustment for educational level, smoking status, alcohol consumption, physical activity, and height. RESULTS: During a mean follow-up of 9.7 years, 14,723 participants died. The lowest risks of death related to BMI were observed at a BMI of 25.3 for men and 24.3 for women. After adjustment for BMI, waist circumference and waist-to-hip ratio were strongly associated with the risk of death. Relative risks among men and women in the highest quintile of waist circumference were 2.05 (95% confidence interval [CI], 1.80 to 2.33) and 1.78 (95% CI, 1.56 to 2.04), respectively, and in the highest quintile of waist-to-hip ratio, the relative risks were 1.68 (95% CI, 1.53 to 1.84) and 1.51 (95% CI, 1.37 to 1.66), respectively. BMI remained significantly associated with the risk of death in models that included waist circumference or waist-to-hip ratio (P<0.001). CONCLUSIONS: These data suggest that both general adiposity and abdominal adiposity are associated with the risk of death and support the use of waist circumference or waist-to-hip ratio in addition to BMI in assessing the risk of death.

Primary brain tumours and specific serum immunoglobulin E: a case-control study nested in the European Prospective Investigation into Cancer and Nutrition cohort.

BACKGROUND: Case-control studies suggest that patients with allergic diseases have a lower risk of developing glioma but not meningioma or schwannoma. However, those data can be differentially biased. Prospective studies with objective measurements of immunologic biomarkers, like immunoglobulin E (IgE), in blood obtained before cancer diagnosis could help to clarify whether an aetiological association exists. METHODS: The present case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) measured specific serum IgE as a biomarker for the most common inhalant allergens in 275 glioma, 175 meningioma and 49 schwannoma cases and 963 matched controls using the ImmunoCAP specific IgE test. Subjects with an IgE level ≥0.35 kUA/l (kilo antibody units per litre) were classified as sensitized by allergens. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by adjusted conditional logistic regression models for each tumour subtype. The effect of dose-response relationship was assessed in five increasing IgE level categories to estimate P-values for trend. RESULTS: The risk of glioma was inversely related to allergic sensitization (OR = 0.73; 95% CI 0.51-1.06), especially pronounced in women (OR = 0.53; 95% CI 0.30-0.95). In dose-response analyses, for high-grade glioma, the lowest OR was observed in sera with the highest IgE levels (P for trend = 0.04). No association was seen for meningioma and schwannoma. CONCLUSION: The results, based on serum samples prospectively collected in a cohort study, provide some support for the hypothesis that individuals with allergic sensitization are at reduced risk of glioma and confirm results from previous case-control studies.

Gene-PUFA interactions and obesity risk.

Although there are indications for modulatory effects of PUFA on associations between SNP and obesity risk, scientific evidence in human subjects is still scarce. The present analyses investigated interaction effects between SNP in candidate genes for obesity and PUFA in erythrocyte membranes on obesity risk. Within the second Bavarian Food Consumption Survey (cross-sectional, population-based), 568 adults provided blood samples. Fatty acid composition of erythrocyte membranes was analysed by means of GC. Genotyping was performed for twenty-one genes, including cytokines, adipokines, neurotransmitters and transcription factors. In addition, plasma IL-6 concentrations were analysed. For the statistical analysis, a logistic regression model assuming additive genetic effects was chosen. About 20 % of the study participants were classified as obese (BMI ≥ 30 kg/m(2)). Several significant gene-PUFA interactions were found, indicating regulatory effects of PUFA by gene variants of IL-2, IL-6, IL-18, TNF receptor family member 1B and 21, leptin receptor and adiponectin on obesity risk. After stratification by genotype, the strongest effects were found for rs2069779 (IL-2) and all tested PUFA as well as for rs1800795 (IL-6) and linoleic or arachidonic acid. The obesity risk of minor allele carriers significantly decreased with increasing fatty acid content. The genetic PUFA-IL-6 interaction was also reflected in plasma IL-6 concentrations. If replicated in a prospective study with sufficient statistical power, the results would indicate a beneficial effect of high PUFA supply for a substantial proportion of the population with respect to obesity risk.

Dietary beta-carotene, vitamin C and E intake and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC).

So far, studies on dietary antioxidant intake, including beta-carotene, vitamin C and vitamin E, and breast cancer risk are inconclusive. Thus, we addressed this question in the European Prospective Investigation into Cancer and Nutrition. During a median follow-up time of 8.8 years, 7,502 primary invasive breast cancer cases were identified. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). All analyses were run stratified by menopausal status at recruitment and, additionally, by smoking status, alcohol intake, use of exogenous hormones and use of dietary supplements. In the multivariate analyses, dietary intake of beta-carotene, vitamin C and E was not associated with breast cancer risk in premenopausal [highest vs. lowest quintile: HR, 1.04 (95% CI, 0.85-1.27), 1.12 (0.92-1.36) and 1.11 (0.84-1.46), respectively] and postmenopausal women [0.93 (0.82-1.04), 0.98 (0.87-1.11) and 0.92 (0.77-1.11), respectively]. However, in postmenopausal women using exogenous hormones, high intake of beta-carotene [highest vs. lowest quintile; HR 0.79 (95% CI, 0.66-0.96), P (trend) 0.06] and vitamin C [0.88 (0.72-1.07), P (trend) 0.05] was associated with reduced breast cancer risk. In addition, dietary beta-carotene was associated with a decreased risk in postmenopausal women with high alcohol intake. Overall, dietary intake of beta-carotene, vitamin C and E was not related to breast cancer risk in neither pre- nor postmenopausal women. However, in subgroups of postmenopausal women, a weak protective effect between beta-carotene and vitamin E from food and breast cancer risk cannot be excluded.

Weight change in later life and risk of death amongst the elderly: the European Prospective Investigation into Cancer and Nutrition-Elderly Network on Ageing and Health study.

OBJECTIVE: Later life weight change and mortality amongst elders. DESIGN: Nested case-control study. SETTING: Six countries from the European Investigation into Cancer and nutrition-Elderly, Network on Ageing and Health. SUBJECTS: A total of 1712 deceased (cases) and 4942 alive (controls) were selected from 34,239 participants, > or = 60 years at enrolment (1992-2000) who were followed-up until March 2007. Annual weight change was estimated as the weight difference from recruitment to the most distant from-date-of-death re-assessment, divided by the respective time. OUTCOME MEASURES: Mortality in relation to weight change was examined using conditional logistic regression. RESULTS: Weight loss > 1 kg year(-1) was associated with statistically significant increased death risk (OR = 1.65; 95% CI: 1.41-1.92) compared to minimal weight change (+/-1 kg year(-1)). Weight gain > 1 kg year(-1) was also associated with increased risk of death (OR = 1.15; 95% CI: 0.98-1.37), but this was evident and statistically significant only amongst overweight/obese (OR = 1.55; 95% CI: 1.17-2.05). In analyses by time interval since weight re-assessment, the association of mortality with weight loss was stronger for the interval proximal (< 1 year) to death (OR = 3.10; 95% CI: 2.03-4.72). The association of mortality with weight gain was stronger at the interval of more than 3 years and statistically significant only amongst overweight/obese (OR = 1.58; 95% CI: 1.07-2.33). Similar patterns were observed regarding death from circulatory diseases and cancer. CONCLUSIONS: In elderly, stable body weight is a predictor of lower subsequent mortality. Weight loss is associated with increased mortality, particularly short-term, probably reflecting underlying nosology. Weight gain, especially amongst overweight/obese elders, is also associated with increased mortality, particularly longer term.