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The World Cancer Research Fund (WCRF) International and the University of Bristol have developed a novel framework for providing an overview of mechanistic pathways and conducting a systematic literature review of the biologically plausible mechanisms underlying exposure–cancer associations. Two teams independently applied the two-stage framework on mechanisms underpinning the association between body fatness and breast cancer to test the framework feasibility and reproducibility as part of a WCRF-commissioned validation study. In stage I, a “hypothesis-free” approach was used to provide an overview of potential intermediate mechanisms between body fatness and breast cancer. Dissimilar rankings of potential mechanisms were observed between the two teams due to different applications of the framework. In stage II, a systematic review was conducted on the insulin-like growth factor 1 receptor (IGF1R) chosen as an intermediate mechanism. Although the studies included differed, both teams found inconclusive evidence for the body fatness–IGF1R association and modest evidence linking IGF1R to breast cancer, and therefore concluded that there is currently weak evidence for IGF1R as mechanism linking body fatness to breast cancer. The framework is a good starting point for conducting systematic reviews by integrating evidence from mechanistic studies on exposure–cancer associations. On the basis of our experience, we provide recommendations for future users. Cancer Epidemiol Biomarkers Prev; 26(11); 1583–94. ©2017 AACR.

The German National Cohort (NAKO) is a multidisciplinary, population-based prospective cohort study that aims to investigate the causes of widespread diseases, identify risk factors and improve early detection and prevention of disease. Specifically, NAKO is designed to identify novel and better characterize established risk and protection factors for the development of cardiovascular diseases, cancer, diabetes, neurodegenerative and psychiatric diseases, musculoskeletal diseases, respiratory and infectious diseases in a random sample of the general population. Between 2014 and 2019, a total of 205,415 men and women aged 19–74 years were recruited and examined in 18 study centres in Germany. The baseline assessment included a face-to-face interview, self-administered questionnaires and a wide range of biomedical examinations. Biomaterials were collected from all participants including serum, EDTA plasma, buffy coats, RNA and erythrocytes, urine, saliva, nasal swabs and stool. In 56,971 participants, an intensified examination programme was implemented. Whole-body 3T magnetic resonance imaging was performed in 30,861 participants on dedicated scanners. NAKO collects follow-up information on incident diseases through a combination of active follow-up using self-report via written questionnaires at 2–3 year intervals and passive follow-up via record linkages. All study participants are invited for re-examinations at the study centres in 4–5 year intervals. Thereby, longitudinal information on changes in risk factor profiles and in vascular, cardiac, metabolic, neurocognitive, pulmonary and sensory function is collected. NAKO is a major resource for population-based epidemiology to identify new and tailored strategies for early detection, prediction, prevention and treatment of major diseases for the next 30 years.

Short-chain fatty acids (SCFAs, mainly acetate, propionate, and butyrate), which are primarily derived from the gut microbiome, may exert anti-inflammatory and immunomodulatory effects, and regulate energy homeostasis. It has been suggested that weight loss may affect SCFA metabolism, but a systematic review of intervention studies is lacking. We aimed to systematically assess the effects of dietary, physical activity–based, and surgical weight-loss interventions among overweight [body mass index (BMI) 25–29.9 kg/m(2))] or obese (BMI ≥30 kg/m(2)) adults (≥18 y) on concentrations of acetate, propionate, butyrate, and total SCFAs in blood, urine, or feces. We conducted a systematic literature search in PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to April 30, 2018 for randomized and nonrandomized weight-loss trials among overweight or obese adults, in which the concentrations of individual and total SCFAs were assessed. A total of 9 studies consisting of 2 randomized parallel-arm trials, 4 crossover trials, and 3 nonrandomized clinical or surgical trials were included. In the majority of studies, changes in fecal SCFA concentrations were assessed, whereas changes in serum SCFAs were reported from 1 trial. Individual and total SCFA concentrations either remained unchanged or decreased significantly following weight loss. Three of the dietary interventions that resulted in decreased SCFA concentrations were low (≤5% of energy) in total carbohydrates. Most of the studies had a high risk of bias. Decreases in SCFA concentrations may accompany weight loss induced by bariatric surgery or dietary restriction among overweight or obese adults, particularly when carbohydrate intake is reduced. However, findings were inconsistent and based on studies with high to unclear risk of bias, and small sample sizes. Because measurements of fecal SCFAs may not be ideal due to limited sample standardization, well-powered trials with repeated blood measurements of SCFAs are required. This review was registered at PROSPERO as CRD42018088716.

Background: Early during the pandemic and the following protective countermeasures, an interest in the consequences of the enacted restriction of social contacts for the mental health of the population arose. Loneliness describes the perceived quality of one’s own contacts and relationships with other individuals. Several prior studies reported associations of loneliness with different somatic and psychiatric disorders. Aim: To analyse the frequency of loneliness and its association with depression and anxiety symptoms in the first wave of the pandemic in Germany in May 2020. Methods: The German National Cohort (NAKO) had recruited and examined 205,000 individuals aged 20 to 69 years in 18 study centres across Germany between 2014 and 2019. The follow-up examination was temporarily stopped due to the pandemic between March and July 2020. In this period a COVID-related questionnaire was developed and sent to all participants. We analysed the first 113,928 questionnaires that were sent back within four weeks in May 2020. Loneliness was assessed with the three-item UCLA Loneliness Scale and anxiety and depression symptoms were collected using the PHQ‑9 and GAD‑7 scales from the Patient Health Questionnaire. Results: Among the NAKO participants, 31.7% reported to be lonely in May 2020. Women and young adults reported more loneliness than men and older adults. With increasing scores of loneliness, the severity of depression and anxiety symptoms also steadily increased. Individuals who were lonely during the pandemic had already reported higher PHQ‑9 and GAD‑7 scores during the baseline examination on average 2.5 years earlier, compared to those who did not feel lonely. Conclusions: Among participants of the German National Cohort, we observed an increase in loneliness during the first wave of the SARS-CoV‑2 pandemic in spring 2020 and a strong relationship of increasing loneliness with decreasing mental health.

BACKGROUND: Arterial hypertension is animportant risk factor for cardiovascular diseases. Epidemiological studies typically perform three consecutive blood pressure measurements. The first measurement is discarded in subsequent analyses, as this value may be strongly affected by previous activities. Due to time constraints the German National Cohort (GNC NAKO) performed only two blood pressure measurements. OBJECTIVES: The present analysis examined the possible effects of methodological differences in blood pressure measurement by comparing the first 101,816 GNC participants (two blood pressure measurements) with those of five German population-based studies (three measurements). MATERIALS AND METHODS: Blood pressure data from participants aged 20 to 79 years from the GNC, the German Health Interview and Examination Survey for Adults by the Robert Koch Institute (DEGS1), and four regional population-based cohort studies (CARLA, HNR, KORA, SHIP) were used to calculate age- and sex-specific mean blood pressure values and hypertension frequencies based on the second blood pressure measurement, the arithmetic mean of the first and second value and of the second and third (the latter not available in the GNC). RESULTS: The mean blood pressure values of the two most recent studies (GNC, DEGS1) were very similar and lower than in the other studies. The difference of the second measurement and the mean of second and third measurement was small (maximum mean difference: 1.5mm Hg systolic blood pressure), but leads to higher estimated hypertension frequencies. CONCLUSIONS: The current results show that using the second blood pressure measurement should be recommended for scientific analyses of GNC data.

BACKGROUND: Caries and periodontitis are highly prevalent worldwide. Because detailed data on these oral diseases were collected within the framework of the German National Cohort (GNC), associations between oral and systemic diseases and conditions can be investigated. OBJECTIVES: The study protocol for the oral examination was designed to ensure a comprehensive collection of dental findings by trained non-dental staff within a limited examination time. At the mid-term of the GNC baseline examination, a first quality evaluation was performed to check the plausibility of results and to propose measures to improve the data quality. MATERIALS AND METHODS: A dental interview, saliva sampling and oral diagnostics were conducted. As part of the level‑1 examination, the number of teeth and prostheses were recorded. As part of the level‑2 examination, detailed periodontal, cariological and functional aspects were examined. All examinations were conducted by trained non-dental personnel. Parameters were checked for plausibility and variable distributions were descriptively analysed. RESULTS: Analyses included data of 57,967 interview participants, 56,913 level‑1 participants and 6295 level‑2 participants. Percentages of missing values for individual clinical parameters assessed in level 1 and level 2 ranged between 0.02 and 3.9%. Results showed a plausible distribution of the data; rarely, implausible values were observed, e.g. for measurements of horizontal and vertical overbite (overjet and overbite). Intra-class correlation coefficients indicated differences in individual parameters between regional clusters, study centres and across different examiners. CONCLUSIONS: he results confirm the feasibility of the study protocol by non-dental personnel and its successful integration into the GNC's overall assessment program. However, rigorous dental support of the study centres is required for quality management.

Caries and periodontitis are highly prevalent worldwide. Because detailed data on these oral diseases were collected within the framework of the German National Cohort (GNC), associations between oral and systemic diseases and conditions can be investigated.The study protocol for the oral examination was designed to ensure a comprehensive collection of dental findings by trained non-dental staff within a limited examination time. At the mid-term of the GNC baseline examination, a first quality evaluation was performed to check the plausibility of results and to propose measures to improve the data quality.A dental interview, saliva sampling and oral diagnostics were conducted. As part of the level‑1 examination, the number of teeth and prostheses were recorded. As part of the level‑2 examination, detailed periodontal, cariological and functional aspects were examined. All examinations were conducted by trained non-dental personnel. Parameters were checked for plausibility and variable distributions were descriptively analysed.Analyses included data of 57,967 interview participants, 56,913 level‑1 participants and 6295 level‑2 participants. Percentages of missing values for individual clinical parameters assessed in level 1 and level 2 ranged between 0.02 and 3.9%. Results showed a plausible distribution of the data; rarely, implausible values were observed, e.g. for measurements of horizontal and vertical overbite (overjet and overbite). Intra-class correlation coefficients indicated differences in individual parameters between regional clusters, study centres and across different examiners.The results confirm the feasibility of the study protocol by non-dental personnel and its successful integration into the GNC's overall assessment program. However, rigorous dental support of the study centres is required for quality management.HINTERGRUND: Karies und Parodontitis sind weltweit hoch prävalente Erkrankungen. Durch ihre Erfassung im Rahmen der NAKO Gesundheitsstudie können Assoziationen zwischen oralen und systemischen Erkrankungen untersucht werden.In einer ersten Qualitätsanalyse zur Halbzeit der NAKO-Basiserhebung wird die Plausibilität der zahnmedizinischen Ergebnisse überprüft. Es werden Maßnahmen zur Verbesserung der Datenqualität vorgeschlagen.Ein zahnmedizinisches Interview, eine Speichelprobengewinnung und eine Befunderhebung wurden durchgeführt. Im Rahmen der Level-1-Untersuchung wurden Zahn- und Prothesenanzahl erfasst. In der Level-2-Untersuchung wurden detaillierte parodontologische, kariologische und funktionelle Befunde erhoben. Alle Untersuchungen wurden von geschultem nichtzahnmedizinischen Personal durchgeführt. Es wurden Plausibilitätsprüfungen durchgeführt sowie Verteilungen deskriptiv dargestellt.In die Analysen gingen Daten von 57.967 Interviewteilnehmer*innen, 56.913 Level-1- und 6295 Level-2-Teilnehmer*innen ein. Der Anteil fehlender Werte lag für die einzelnen Parameter der Level-1- und Level-2-Untersuchungen zwischen 0,02 % und 3,9 %. Die Parameter zeigten eine plausible Verteilung; vereinzelt wurden unplausible Werte beobachtet, z. B. beim horizontalen und vertikalen Überbiss (Overjet und Overbite). Anhand der Intraklassenkorrelationskoeffizienten wurden für die einzelnen Parameter Unterschiede zwischen regionalen Clustern, den Studienzentren und verschiedenen Untersucher*innen nachgewiesen.Die bisherigen Ergebnisse bestätigten die Umsetzbarkeit des Studienprotokolls durch nichtzahnmedizinisches Personal und die erfolgreiche Integration in das Untersuchungsprogramm der NAKO Gesundheitsstudie. Die Studienzentren benötigen eine intensive zahnmedizinische Betreuung für das Qualitätsmanagement.

BACKGROUND: The German National Cohort (NAKO) is an interdisciplinary health study aimed at elucidating causes for common chronic diseases and detecting their preclinical stages. This article provides an overview of design, methods, participation in the examinations, and their quality assurance based on the midterm baseline dataset (MBD) of the recruitment. METHODS: More than 200,000 women and men aged 20-69 years derived from random samples of the German general population were recruited in 18 study centers (2014-2019). The data collection comprised physical examinations, standardized interviews and questionnaires, and the collection of biomedical samples for all participants (level 1). At least 20% of all participants received additional in-depth examinations (level 2), and 30,000 received whole-body magnet resonance imaging (MRI). Additional information will be collected through secondary data sources such as medical registries, health insurances, and pension funds. This overview is based on the MBD, which included 101,839 participants, of whom 11,371 received an MRI. RESULTS: The mean response proportion was 18%. The participation in the examinations was high with most of the modules performed by over 95%. Among MRI participants, 96% completed all 12 MRI sequences. More than 90% of the participants agreed to the use of complementary secondary and registry data. DISCUSSION: Individuals selected for the NAKO were willing to participate in all examinations despite the time-consuming program. The NAKO provides a central resource for population-based epidemiologic research and will contribute to developing innovative strategies for prevention, screening and prediction of chronic diseases.

BACKGROUND: In epidemiologic studies, standardised measurement of socio-demographic and employment-related factors is becoming increasingly important, as variables such as gender, age, education or employment status are factors influencing health and disease risks. AIMS: The article gives an overview of the scientific background and assessment of socio-demographic factors in the German National Cohort Study. In addition, the distribution of individual characteristics in the cohort as well as relationships with health-related measures are presented by way of example. MATERIAL AND METHODS: The analysis is based on the data of the first half of the baseline survey (n = 101,724). On this basis, we present the distribution of key socio-demographic characteristics and analyse relationships with exemplary selected health indicators (body mass index, self-reported health) to assess the validity of socio-demographic data measurements. RESULTS: On average, study participants were 52.0 years old (SD = 12.4). Of the participants, 53.6% were women, 54.3% had high education, 60.1% were married and 72% were employed while 3.4% were unemployed. Well-established correlations between socio-demographic factors and health could be reproduced with the German National Cohort data. For example, low education, old age and unemployment were associated with an increased prevalence of obesity and poor self-reported health. DISCUSSION: The German National Cohort provides a comprehensive measurement of socio-demographic characteristics. Combined with a wide range of health data and the longitudinal measurements available in the future, this opens up new opportunities for health science and social epidemiological research in Germany.

BACKGROUND: Noise annoyance is associated with adverse health-related conditions and reduced wellbeing. Thereby, subjective noise annoyance depends on the objective noise exposure and is modified by personal and regional factors. OBJECTIVE: How many participants of the German National Cohort Study (GNC; NAKO Gesundheitsstudie) were annoyed by transportation noise during nighttime and what factors were associated with noise annoyance? MATERIALS AND METHODS: This cross-sectional analysis included 86,080 participants from 18 study centers, examined from 2014 to 2017. We used multinomial logistic regression to investigate associations of personal and regional factors to noise annoyance (slightly/moderately or strongly/extremely annoyed vs. not annoyed) mutually adjusting for all factors in the model. RESULTS: Two thirds of participants were not annoyed by transportation noise during nighttime and one in ten reported strong/extreme annoyance with highest percentages for the study centers Berlin-Mitte and Leipzig. The strongest associations were seen for factors related to the individual housing situation like the bedroom being positioned towards a major road (OR of being slightly/moderately annoyed: 4.26 [95% CI: 4.01;4.52]; OR of being strongly/extremely annoyed: 13.36 [95% CI: 12.47;14.32]) compared to a garden/inner courtyard. Participants aged 40-60 years and those in low- and medium-income groups reported greater noise annoyance compared to younger or older ones and those in the high-income group. CONCLUSION: In this study from Germany, transportation noise annoyance during nighttime varied by personal and regional factors.

Physical fitness is defined as an individual's ability to be physically active. The main components are cardiorespiratory fitness (CRF), muscle strength, and flexibility. Regardless of physical activity level, physical fitness is an important determinant of morbidity and mortality.The aim of the current study was to describe the physical fitness assessment methodology in the German National Cohort (NAKO) and to present initial descriptive results in a subsample of the cohort.In the NAKO, hand grip strength (GS) and CRF as physical fitness components were assessed at baseline using a hand dynamometer and a submaximal bicycle ergometer test, respectively. Maximum oxygen uptake (VO2max) was estimated as a result of the bicycle ergometer test. The results of a total of 99,068 GS measurements and 3094 CRF measurements are based on a data set at halftime of the NAKO baseline survey (age 20-73 years, 47% men).Males showed higher values of physical fitness compared to women (males: GS = 47.8 kg, VO2max = 36.4 ml·min-1 · kg-1; females: GS = 29.9 kg, VO2max = 32.3 ml · min-1 · kg-1). GS declined from the age of 50 onwards, whereas VO2max levels decreased continuously between the age groups of 20-29 and ≥60 years. GS and VO2max showed a linear positive association after adjustment for body weight (males β = 0.21; females β = 0.35).These results indicate that the physical fitness measured in the NAKO are comparable to other population-based studies. Future analyses in this study will focus on examining the independent relations of GS and CRF with risk of morbidity and mortality.

BACKGROUND: The German National Cohort (NAKO) is an interdisciplinary health study aimed at elucidating causes for common chronic diseases and detecting their preclinical stages. This article provides an overview of design, methods, participation in the examinations, and their quality assurance based on the midterm baseline dataset (MBD) of the recruitment. METHODS: More than 200,000 women and men aged 20-69 years derived from random samples of the German general population were recruited in 18 study centers (2014-2019). The data collection comprised physical examinations, standardized interviews and questionnaires, and the collection of biomedical samples for all participants (level 1). At least 20% of all participants received additional in-depth examinations (level 2), and 30,000 received whole-body magnet resonance imaging (MRI). Additional information will be collected through secondary data sources such as medical registries, health insurances, and pension funds. This overview is based on the MBD, which included 101,839 participants, of whom 11,371 received an MRI. RESULTS: The mean response proportion was 18%. The participation in the examinations was high with most of the modules performed by over 95%. Among MRI participants, 96% completed all 12 MRI sequences. More than 90% of the participants agreed to the use of complementary secondary and registry data. DISCUSSION: Individuals selected for the NAKO were willing to participate in all examinations despite the time-consuming program. The NAKO provides a central resource for population-based epidemiologic research and will contribute to developing innovative strategies for prevention, screening and prediction of chronic diseases.

In epidemiologic studies, standardised measurement of socio-demographic and employment-related factors is becoming increasingly important, as variables such as gender, age, education or employment status are factors influencing health and disease risks.The article gives an overview of the scientific background and assessment of socio-demographic factors in the German National Cohort Study. In addition, the distribution of individual characteristics in the cohort as well as relationships with health-related measures are presented by way of example.The analysis is based on the data of the first half of the baseline survey (n = 101,724). On this basis, we present the distribution of key socio-demographic characteristics and analyse relationships with exemplary selected health indicators (body mass index, self-reported health) to assess the validity of socio-demographic data measurements.On average, study participants were 52.0 years old (SD = 12.4). Of the participants, 53.6% were women, 54.3% had high education, 60.1% were married and 72% were employed while 3.4% were unemployed. Well-established correlations between socio-demographic factors and health could be reproduced with the German National Cohort data. For example, low education, old age and unemployment were associated with an increased prevalence of obesity and poor self-reported health.The German National Cohort provides a comprehensive measurement of socio-demographic characteristics. Combined with a wide range of health data and the longitudinal measurements available in the future, this opens up new opportunities for health science and social epidemiological research in Germany.

BACKGROUND: The German National Cohort (NAKO) is an interdisciplinary health study aimed at elucidating causes for common chronic diseases and detecting their preclinical stages. This article provides an overview of design, methods, participation in the examinations, and their quality assurance based on the midterm baseline dataset (MBD) of the recruitment. METHODS: More than 200,000 women and men aged 20–69 years derived from random samples of the German general population were recruited in 18 study centers (2014–2019). The data collection comprised physical examinations, standardized interviews and questionnaires, and the collection of biomedical samples for all participants (level 1). At least 20% of all participants received additional in-depth examinations (level 2), and 30,000 received whole-body magnet resonance imaging (MRI). Additional information will be collected through secondary data sources such as medical registries, health insurances, and pension funds. This overview is based on the MBD, which included 101,839 participants, of whom 11,371 received an MRI. RESULTS: The mean response proportion was 18%. The participation in the examinations was high with most of the modules performed by over 95%. Among MRI participants, 96% completed all 12 MRI sequences. More than 90% of the participants agreed to the use of complementary secondary and registry data. DISCUSSION: Individuals selected for the NAKO were willing to participate in all examinations despite the time-consuming program. The NAKO provides a central resource for population-based epidemiologic research and will contribute to developing innovative strategies for prevention, screening and prediction of chronic diseases. HINTERGRUND: Die NAKO Gesundheitsstudie ist ein bundesweites interdisziplinäres Forschungsvorhaben mit dem Ziel, die Ursachen für chronische Krankheiten und deren vorklinische Stadien zu untersuchen. Der Artikel gibt einen Überblick über das Studiendesign, die Methoden, die Teilnahme an den Untersuchungen und ihre Qualitätssicherung zur Halbzeit der Basiserhebung. METHODEN: Für die Basiserhebung wurden mehr als 200.000 Frauen und Männer im Alter von 20–69 Jahren aus Zufallsstichproben der Allgemeinbevölkerung in 18 Studienzentren rekrutiert (2014–2019). Die Basiserhebung beinhaltet Untersuchungen, Befragungen und Biomaterialien für alle Teilnehmerinnen und Teilnehmer (Level 1), ein erweitertes Programm für mindestens 20 % (Level 2) und eine Magnetresonanztomografie (MRT) für 30.000 Teilnehmerinnen und Teilnehmer. Sekundär- und Registerdaten werden über Krankheitsregister, Kranken- und Rentenversicherungen erhoben. Die Auswertung bezieht die Datenbasis zur Halbzeit der Basiserhebung mit 101.839 Teilnehmerinnen und Teilnehmern ein, davon 11.371 mit einer MRT-Untersuchung. ERGEBNISSE: Die mittlere Responsequote zur Halbzeit betrug insgesamt 18 %. Die Teilnahme an den Untersuchungen lag überwiegend bei mehr als 95 %. Bei 96 % der MRT-Teilnehmerinnen und Teilnehmer konnten alle 12 MRT-Sequenzen vollständig durchgeführt werden. Der Erschließung und wissenschaftlichen Nutzung ergänzender Sekundär- und Registerdaten stimmten mehr als 90 % der Teilnehmerinnen und Teilnehmer zu. DISKUSSION: Die Bereitschaft, möglichst alle Untersuchungsmodule durchzuführen, war trotz des zeitlichen Aufwandes außerordentlich hoch. Dadurch wird die NAKO zu einer zentralen Ressource für die epidemiologische Forschung in Deutschland. Sie wird es ermöglichen, neue Strategien zur Früherkennung, Vorhersage und Primärprävention chronischer Krankheiten zu entwickeln.

Background: Bile acids have been proposed to promote colon carcinogenesis. However, there are limited prospective data on circulating bile acid levels and colon cancer risk in humans. Methods: Associations between prediagnostic plasma levels of 17 primary, secondary, and tertiary bile acid metabolites (conjugated and unconjugated) and colon cancer risk were evaluated in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Bile acid levels were quantified by tandem mass spectrometry in samples from 569 incident colon cancer cases and 569 matched controls. Multivariable logistic regression analyses were used to estimate odds ratios (ORs) for colon cancer risk across quartiles of bile acid concentrations. Results: Positive associations were observed between colon cancer risk and plasma levels of seven conjugated bile acid metabolites: the primary bile acids glycocholic acid (ORquartile 4 vs quartile 1= 2.22, 95% confidence interval [CI] = 1.52 to 3.26), taurocholic acid (OR = 1.78, 95% CI = 1.23 to 2.58), glycochenodeoxycholic acid (OR = 1.68, 95% CI = 1.13 to 2.48), taurochenodeoxycholic acid (OR = 1.62, 95% CI = 1.11 to 2.36), and glycohyocholic acid (OR = 1.65, 95% CI = 1.13 to 2.40), and the secondary bile acids glycodeoxycholic acid (OR = 1.68, 95% CI = 1.12 to 2.54) and taurodeoxycholic acid (OR = 1.54, 95% CI = 1.02 to 2.31). By contrast, unconjugated bile acids and tertiary bile acids were not associated with risk. Conclusions: This prospective study showed that prediagnostic levels of certain conjugated primary and secondary bile acids were positively associated with risk of colon cancer. Our findings support experimental data to suggest that a high bile acid load is colon cancer promotive. © 2020 The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Hintergrund: Die NAKO Gesundheitsstudie ist ein bundesweites interdisziplinäres Forschungsvorhaben mit dem Ziel, die Ursachen für chronische Krankheiten und deren vorklinische Stadien zu untersuchen. Der Artikel gibt einen Überblick über das Studiendesign, die Methoden, die Teilnahme an den Untersuchungen und ihre Qualitätssicherung zur Halbzeit der Basiserhebung. Methoden: Für die Basiserhebung wurden mehr als 200.000 Frauen und Männer im Alter von 20-69 Jahren aus Zufallsstichproben der Allgemeinbevölkerung in 18 Studienzentren rekrutiert (2014-2019). Die Basiserhebung beinhaltet Untersuchungen, Befragungen und Biomaterialien für alle Teilnehmerinnen und Teilnehmer (Level 1), ein erweitertes Programm für mindestens 20 % (Level 2) und eine Magnetresonanztomografie (MRT) für 30.000 Teilnehmerinnen und Teilnehmer. Sekundär- und Registerdaten werden über Krankheitsregister, Kranken- und Rentenversicherungen erhoben. Die Auswertung bezieht die Datenbasis zur Halbzeit der Basiserhebung mit 101.839 Teilnehmerinnen und Teilnehmern ein, davon 11.371 mit einer MRT-Untersuchung. Ergebnisse: Die mittlere Responsequote zur Halbzeit betrug insgesamt 18 %. Die Teilnahme an den Untersuchungen lag überwiegend bei mehr als 95 %. Bei 96 % der MRT-Teilnehmerinnen und Teilnehmer konnten alle 12 MRT-Sequenzen vollständig durchgeführt werden. Der Erschließung und wissenschaftlichen Nutzung ergänzender Sekundär- und Registerdaten stimmten mehr als 90 % der Teilnehmerinnen und Teilnehmer zu. Diskussion: Die Bereitschaft, möglichst alle Untersuchungsmodule durchzuführen, war trotz des zeitlichen Aufwandes außerordentlich hoch. Dadurch wird die NAKO zu einer zentralen Ressource für die epidemiologische Forschung in Deutschland. Sie wird es ermöglichen, neue Strategien zur Früherkennung, Vorhersage und Primärprävention chronischer Krankheiten zu entwickeln.

BACKGROUND: In epidemiologic studies, standardised measurement of socio-demographic and employment-related factors is becoming increasingly important, as variables such as gender, age, education or employment status are factors influencing health and disease risks. AIMS: The article gives an overview of the scientific background and assessment of socio-demographic factors in the German National Cohort Study. In addition, the distribution of individual characteristics in the cohort as well as relationships with health-related measures are presented by way of example. MATERIAL AND METHODS: The analysis is based on the data of the first half of the baseline survey (n = 101,724). On this basis, we present the distribution of key socio-demographic characteristics and analyse relationships with exemplary selected health indicators (body mass index, self-reported health) to assess the validity of socio-demographic data measurements. RESULTS: On average, study participants were 52.0 years old (SD = 12.4). Of the participants, 53.6% were women, 54.3% had high education, 60.1% were married and 72% were employed while 3.4% were unemployed. Well-established correlations between socio-demographic factors and health could be reproduced with the German National Cohort data. For example, low education, old age and unemployment were associated with an increased prevalence of obesity and poor self-reported health. DISCUSSION: The German National Cohort provides a comprehensive measurement of socio-demographic characteristics. Combined with a wide range of health data and the longitudinal measurements available in the future, this opens up new opportunities for health science and social epidemiological research in Germany. HINTERGRUND: In epidemiologischen Studien ist die standardisierte Erfassung soziodemografischer Merkmale von hoher Bedeutung, da Variablen wie Geschlecht, Alter, Bildung oder Erwerbsstatus wichtige Einflussfaktoren auf Gesundheitschancen und Krankheitsrisiken darstellen. In der NAKO Gesundheitsstudie werden zentrale Faktoren aus diesem Themenbereich berücksichtigt. ZIEL DER ARBEIT: Der Beitrag gibt einen Überblick über den wissenschaftlichen Hintergrund und die konkrete Erhebung soziodemografischer Angaben in der NAKO. Zudem werden die Verteilung einzelner Merkmale sowie Zusammenhänge mit gesundheitsassoziierten Maßen exemplarisch vorgestellt. MATERIAL UND METHODEN: Anhand der Daten zur Halbzeit der Basiserhebung (n = 101.724) wurde die Verteilung soziodemografischer Merkmale dargestellt und Zusammenhänge mit beispielhaft ausgewählten Gesundheitsindikatoren (Body-Mass-Index, selbst berichtete Gesundheit) analysiert, um die Validität der Messung soziodemografischer Angaben zu beurteilen. ERGEBNISSE: Das mittlere Alter der Teilnehmenden lag bei 52,0 Jahren (SD = 12,4). 53,6 % der Teilnehmenden waren Frauen, 54,3 % hatten einen hohen Bildungsabschluss, 60,1 % waren verheiratet zusammenlebend, 72,0 % erwerbstätig und 3,4 % erwerbslos. Bekannte Zusammenhänge zwischen Soziodemografie und Gesundheit konnten reproduziert werden. So waren niedrige Bildung, hohes Alter und Erwerbslosigkeit mit einer erhöhten Häufigkeit von Adipositas und schlechter selbst berichteter Gesundheit assoziiert. DISKUSSION: Die NAKO Gesundheitsstudie erhebt viele soziodemografische Merkmale. In Kombination mit der Fülle an Gesundheitsdaten und dem Längsschnittdesign ergeben sich so neue Möglichkeiten für die gesundheitswissenschaftliche und sozialepidemiologische Forschung in Deutschland.

BACKGROUND: Caries and periodontitis are highly prevalent worldwide. Because detailed data on these oral diseases were collected within the framework of the German National Cohort (GNC), associations between oral and systemic diseases and conditions can be investigated. OBJECTIVES: The study protocol for the oral examination was designed to ensure a comprehensive collection of dental findings by trained non-dental staff within a limited examination time. At the mid-term of the GNC baseline examination, a first quality evaluation was performed to check the plausibility of results and to propose measures to improve the data quality. MATERIALS AND METHODS: A dental interview, saliva sampling and oral diagnostics were conducted. As part of the level‑1 examination, the number of teeth and prostheses were recorded. As part of the level‑2 examination, detailed periodontal, cariological and functional aspects were examined. All examinations were conducted by trained non-dental personnel. Parameters were checked for plausibility and variable distributions were descriptively analysed. RESULTS: Analyses included data of 57,967 interview participants, 56,913 level‑1 participants and 6295 level‑2 participants. Percentages of missing values for individual clinical parameters assessed in level 1 and level 2 ranged between 0.02 and 3.9%. Results showed a plausible distribution of the data; rarely, implausible values were observed, e.g. for measurements of horizontal and vertical overbite (overjet and overbite). Intra-class correlation coefficients indicated differences in individual parameters between regional clusters, study centres and across different examiners. CONCLUSIONS: The results confirm the feasibility of the study protocol by non-dental personnel and its successful integration into the GNC’s overall assessment program. However, rigorous dental support of the study centres is required for quality management. HINTERGRUND:Karies und Parodontitis sind weltweit hoch prävalente Erkrankungen. Durch ihre Erfassung im Rahmen der NAKO Gesundheitsstudie können Assoziationen zwischen oralen und systemischen Erkrankungen untersucht werden. FRAGESTELLUNG: In einer ersten Qualitätsanalyse zur Halbzeit der NAKO-Basiserhebung wird die Plausibilität der zahnmedizinischen Ergebnisse überprüft. Es werden Maßnahmen zur Verbesserung der Datenqualität vorgeschlagen. MATERIAL UND METHODEN: Ein zahnmedizinisches Interview, eine Speichelprobengewinnung und eine Befunderhebung wurden durchgeführt. Im Rahmen der Level-1-Untersuchung wurden Zahn- und Prothesenanzahl erfasst. In der Level-2-Untersuchung wurden detaillierte parodontologische, kariologische und funktionelle Befunde erhoben. Alle Untersuchungen wurden von geschultem nichtzahnmedizinischen Personal durchgeführt. Es wurden Plausibilitätsprüfungen durchgeführt sowie Verteilungen deskriptiv dargestellt. ERGEBNISSE: In die Analysen gingen Daten von 57.967 Interviewteilnehmer*innen, 56.913 Level-1- und 6295 Level-2-Teilnehmer*innen ein. Der Anteil fehlender Werte lag für die einzelnen Parameter der Level-1- und Level-2-Untersuchungen zwischen 0,02 % und 3,9 %. Die Parameter zeigten eine plausible Verteilung; vereinzelt wurden unplausible Werte beobachtet, z. B. beim horizontalen und vertikalen Überbiss (Overjet und Overbite). Anhand der Intraklassenkorrelationskoeffizienten wurden für die einzelnen Parameter Unterschiede zwischen regionalen Clustern, den Studienzentren und verschiedenen Untersucher*innen nachgewiesen. DISKUSSION: Die bisherigen Ergebnisse bestätigten die Umsetzbarkeit des Studienprotokolls durch nichtzahnmedizinisches Personal und die erfolgreiche Integration in das Untersuchungsprogramm der NAKO Gesundheitsstudie. Die Studienzentren benötigen eine intensive zahnmedizinische Betreuung für das Qualitätsmanagement.

igh levels of adiposity in the population have a major impact on various diseases, but previous epidemiologic studies have largely been restricted to simple anthropometric measures such as the body mass index (BMI), an imperfect predictor of disease risk. There is a critical need for the use of improved measures of relative weight and body composition in large-scale, population-based research. The current article presents initial descriptive results of body composition and fat distribution based on the midterm baseline dataset of the German National Cohort, which included 101,817 participants who were examined in 18 study centers in Germany between March 2014 and March 2017. The anthropometric measures encompassed body weight, height, waist and hip circumference, bioelectrical impedance analysis (BIA), sonography of abdominal adipose tissue, 3D-body scanning, and magnetic resonance imaging. BMI analyses showed that 46.2% of men and 29.7% of women were overweight and 23.5% of men and 21.2% of women were obese. On average, women in almost all age groups demonstrated more subcutaneous adipose tissue layer thickness than men. The mean values of visceral adipose tissue layer thickness, on the other hand, were higher among men than among women in all age groups and increased continuously across age groups in both sexes. The comprehensive assessment of body composition and fat distribution provides novel future opportunities for detailed epidemiologic analyses of overweight and adiposity in relation to the development of chronic diseases.

Die körperliche Fitness ist das Maß für die individuelle Fähigkeit, körperlich aktiv zu sein. Ihre wesentlichen Komponenten sind die kardiorespiratorische Fitness (Cardiorespiratory Fitness, CRF), die Muskelkraft und die Beweglichkeit. Neben der körperlichen Aktivität ist die körperliche Fitness ein wesentlicher Prädiktor für Morbidität und Mortalität. Ziel der Arbeit sind die Beschreibung der Erhebungsmethoden körperlicher Fitness in der NAKO Gesundheitsstudie und die Darstellung erster deskriptiver Ergebnisse. In der NAKO-Basiserhebung wurden die maximale Handgreifkraft (Grip Strength, GS) und die CRF als Komponenten der körperlichen Fitness über ein Handdynamometer bzw. über einen Fahrradergometertest mit submaximaler Belastung erhoben. Daraus wurde die maximale Sauerstoffaufnahme (VO2max) zur Beurteilung der CRF abgeleitet. Die Ergebnisse von insgesamt 99.068 GS-Messungen und 3094 Messungen der CRF beruhen auf einem Datensatz zur Halbzeit der Basiserhebung der NAKO (Alter 20–73 Jahre, 47 % Männer). Männer zeigten im Vergleich zu Frauen höhere Werte der körperlichen Fitness (Männer: GS = 47,8 kg, VO2max = 36,4 ml·min−1 · kg−1; Frauen: GS = 29,9 kg, VO2max = 32,3 ml·min−1 · kg−1). Ungefähr ab dem 50. Lebensjahr konnte ein Rückgang der GS verzeichnet werden, wohingegen die CRF ab der Altersgruppe 20–29 Jahre bis zu den ≥60-Jährigen kontinuierlich abfiel. Die GS und die VO2max zeigten nach Korrektur für das Körpergewicht einen linear positiven Zusammenhang (Männer β = 0,21; Frauen β = 0,35). Die Analysen zeigten eine gute Übereinstimmung der Verteilung der körperlichen Fitness in der NAKO im Vergleich zu anderen bevölkerungsbasierten Studien. Zukünftige Auswertungen werden insbesondere die unabhängige Bedeutung der GS und CRF bei der Prädiktion von Morbidität und Mortalität beleuchten. Physical fitness is defined as an individual’s ability to be physically active. The main components are cardiorespiratory fitness (CRF), muscle strength, and flexibility. Regardless of physical activity level, physical fitness is an important determinant of morbidity and mortality. The aim of the current study was to describe the physical fitness assessment methodology in the German National Cohort (NAKO) and to present initial descriptive results in a subsample of the cohort. In the NAKO, hand grip strength (GS) and CRF as physical fitness components were assessed at baseline using a hand dynamometer and a submaximal bicycle ergometer test, respectively. Maximum oxygen uptake (VO2max) was estimated as a result of the bicycle ergometer test. The results of a total of 99,068 GS measurements and 3094 CRF measurements are based on a data set at halftime of the NAKO baseline survey (age 20–73 years, 47% men). Males showed higher values of physical fitness compared to women (males: GS = 47.8 kg, VO2max = 36.4 ml·min−1 · kg−1; females: GS = 29.9 kg, VO2max = 32.3 ml · min−1 · kg−1). GS declined from the age of 50 onwards, whereas VO2max levels decreased continuously between the age groups of 20–29 and ≥60 years. GS and VO2max showed a linear positive association after adjustment for body weight (males β = 0.21; females β = 0.35). These results indicate that the physical fitness measured in the NAKO are comparable to other population-based studies. Future analyses in this study will focus on examining the independent relations of GS and CRF with risk of morbidity and mortality.

Hintergrund Lärmbelästigung geht mit gesundheitlicher Beeinträchtigung und reduziertem Wohlbefinden einher. Die subjektive Lärmbelästigung steht im Zusammenhang mit der objektiven Lärmbelastung sowie individuellen und regionalen Faktoren. Fragestellung Wie viele Teilnehmende der NAKO Gesundheitsstudie fühlen sich durch nächtlichen Verkehrslärm belästigt und welche Faktoren stehen damit im Zusammenhang? Material und Methoden Diese Querschnittsanalyse basiert auf Daten von 86.080 NAKO-Teilnehmenden aus 18 Studienzentren, die von 2014 bis 2017 untersucht wurden. Um die Beziehungen zwischen individuellen und regionalen Faktoren und Verkehrslärmbelästigung in den Kategorien nicht belästigt, leicht/mittel und stark/sehr stark belästigt zu untersuchen, wurden multinomiale logistische Regressionsmodelle mit wechselseitiger Adjustierung der Faktoren verwendet. Ergebnisse Zwei Drittel der Teilnehmenden fühlten sich nicht durch Verkehrslärm belästigt; jeder Zehnte berichtete von starker/sehr starker Belästigung, mit den höchsten Anteilen in Berlin-Mitte und Leipzig. Die stärksten Assoziationen mit Lärmbelästigung wurden für Faktoren der individuellen Wohnsituation beobachtet, wie z. B. die Position des Schlafraums zur Hauptstraße (OR für leicht/mittel belästigt: 4,26 [95 % KI: 4,01; 4,52]; OR für stark/sehr stark belästigt: 13,36 [95 % KI: 12,47; 14,32] im Vergleich zu Garten/Innenhof). Teilnehmende im Alter von 40–60 Jahren oder der mittleren und niedrigen Einkommensklasse fühlten sich eher durch Verkehrslärm belästigt als jüngere bzw. ältere Teilnehmende oder solche mit hoher Einkommensklasse. Diskussion Teilnehmende der NAKO Gesundheitsstudie wiesen Unterschiede in der Belästigung durch nächtlichen Verkehrslärm in Bezug auf individuelle und regionale Faktoren auf., Background Noise annoyance is associated with adverse health-related conditions and reduced wellbeing. Thereby, subjective noise annoyance depends on the objective noise exposure and is modified by personal and regional factors. Objective How many participants of the German National Cohort Study (GNC; NAKO Gesundheitsstudie) were annoyed by transportation noise during nighttime and what factors were associated with noise annoyance? Materials and methods This cross-sectional analysis included 86,080 participants from 18 study centers, examined from 2014 to 2017. We used multinomial logistic regression to investigate associations of personal and regional factors to noise annoyance (slightly/moderately or strongly/extremely annoyed vs. not annoyed) mutually adjusting for all factors in the model. Results Two thirds of participants were not annoyed by transportation noise during nighttime and one in ten reported strong/extreme annoyance with highest percentages for the study centers Berlin-Mitte and Leipzig. The strongest associations were seen for factors related to the individual housing situation like the bedroom being positioned towards a major road (OR of being slightly/moderately annoyed: 4.26 [95% CI: 4.01;4.52]; OR of being strongly/extremely annoyed: 13.36 [95% CI: 12.47;14.32]) compared to a garden/inner courtyard. Participants aged 40–60 years and those in low- and medium-income groups reported greater noise annoyance compared to younger or older ones and those in the high-income group. Conclusion In this study from Germany, transportation noise annoyance during nighttime varied by personal and regional factors.

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HINTERGRUND: Arterielle Hypertonie ist einwichtiger Risikofaktor für Herz-Kreislauf-Er-krankungen. Epidemiologische Studien führen meist drei konsekutive Blutdruckmessungen durch. Der 1. Messwert wird für Auswertungen verworfen, da dieser am stärksten durch vorhergehende Aktivitäten beeinflusst sein kann. Aus zeitlichen Gründen wurden in der NAKO Gesundheitsstudie nur zwei Messungen durchgeführt. FRAGESTELLUNG: Die vorliegende Analyse untersucht Auswirkungen methodischer Unterschiede bei der Blutdruckmessungauf die Hypertoniehäufigkeit und mittlere Blutdruckwerte anhand eines Vergleichsder ersten Hälfte der NAKO-Teilnehmenden(nur 2 Messungen) mit 5 deutschen populationsbasierten Studien (3 Messungen). MATERIAL UND METHODEN: Es wurden Daten der Teilnehmenden aus der NAKO (erste 101.816 Personen), der bundesweiten Studie zur Gesundheit Erwachsener des Robert Koch-Instituts (DEGS1) und aus 4 regionalen populationsbasierten Kohortenstudien (CARLA, HNR, KORA, SHIP) analysiert. Alters- und geschlechtsspezifische mittlere Blutdruckwerte und Hypertoniehäufigkeiten wurden auf Basis des 2. Messwertes, des Mittelwerts aus 1. und 2. sowie aus 2. und 3. Messung berechnet. ERGEBNISSE: Die mittleren Blutdruckwerte der beiden aktuellsten Studien (NAKO und DEGS1) sind sehr ähnlich und niedriger als in den anderen Studien. Die Differenz zwischen dem 2. Messwert und dem Mittelwert aus 2. und 3. Messung ist gering (maximale mittlere Abweichung: 1,5mmHg systolisch), jedoch ist die mittels des 2. Messwertes berechnete Hypertoniehäufigkeit der Bevölkerung höher als bei Verwendung des Mittelwertsaus 2. und 3. Messung. DISKUSSION: Die Ergebnisse der vorliegenden Analyse zeigen, dass für die wissenschaftliche Auswertung der NAKO-Daten die Verwendung des 2. Blutdruckmesswerts zu empfehlen ist. BACKGROUND: Arterial hypertension is an important risk factor for cardiovascular diseases. Epidemiological studies typically perform three consecutive blood pressure measurements. The first measurement is discarded in subsequent analyses, as this value may be strongly affected by previous activities. Due to time constraints the German National Cohort (GNC NAKO) performed only two blood pressure measurements. OBJECTIVES. The present analysis examined the possible effects of methodological differences in blood pressure measurement by comparing the first 101,816 GNC participants (two blood pressure measurements) with those of five German population-based studies (three measurements). MATERIALS AND METHODS: Blood pressure data from participants aged 20 to 79 years from the GNC, the German Health Interview and Examination Survey for Adults by the Robert Koch Institute (DEGS1), and four regional population-based cohort studies (CARLA, HNR, KORA, SHIP) were used to calculate age-and sex-specific mean blood pressure values and hypertension frequencies based on the second blood pressure measurement, the arithmetic mean of the first and second value and of the second and third (the latter not available in the GNC). RESULTS: The mean blood pressure values of the two most recent studies (GNC, DEGS1) were very similar and lower than in the other studies. The difference of the second measurement and the mean of second and third measurement was small (maximum mean difference: 1.5mmHg systolic blood pressure), but leads to higher estimated hypertension frequencies. CONCLUSIONS: The current results show that using the second blood pressure measurement should be recommended for scientific analyses of GNC data.

BACKGROUND Obesity and associated metabolic disorders are related to impairments of the intestinal barrier. OBJECTIVE We examined lactulose:mannitol (Lac:Man) permeability in obese individuals with and without liver steatosis undergoing a weight-reduction program to test whether an effective weight-loss program improves gut barrier function and whether obese patients with or without liver steatosis differ in this function. DESIGN Twenty-seven adult, nondiabetic individuals [mean ± SD body mass index (BMI; in kg/m2): 43.7 ± 5.2; 78% with moderate or severe liver steatosis] were included in the follow-up intervention study (n = 13 by month 12). All patients reduced their weight to a mean ± SD BMI of 36.4 ± 5.1 within 12 mo. We assessed barrier functions by the oral Lac:Man and the fecal zonulin tests. Insulin resistance was assessed by the homeostatic model assessment index (HOMA), and liver steatosis by sonography and the fatty liver index (FLI). RESULTS The Lac:Man ratio and circulating interleukin (IL) 6 concentration decreased during intervention from 0.080 (95% CI: 0.073, 0.093) to 0.027 (95% CI: 0.024, 0.034; P < 0.001) and from 4.2 ± 1.4 to 2.8 ± 1.6 pg/mL (P < 0.01), respectively. At study start, the Lac:Man ratio was higher in patients with moderate or severe steatosis than in those without any steatosis (P < 0.001). The Lac:Man ratio tended to correlate with HOMA (ρ = 0.55, P = 0.052), which correlated with FLI (ρ = 0.75, P < 0.01). A multiple-regression analysis led to a final model explaining FLI best through BMI, waist circumference, and the Lac:Man ratio. CONCLUSIONS Intestinal permeability is increased in obese patients with steatosis compared with obese patients without. The increased permeability fell to within the previously reported normal range after weight reduction. The data suggest that a leaky gut barrier is linked with liver steatosis and could be a new target for future steatosis therapies. This trial was registered at clinicaltrials.gov as NCT01344525.

Background Bile acids have been proposed to promote colon carcinogenesis. However, there are limited prospective data on circulating bile acid levels and colon cancer risk in humans. Methods Associations between prediagnostic plasma levels of 17 primary, secondary, and tertiary bile acid metabolites (conjugated and unconjugated) and colon cancer risk were evaluated in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Bile acid levels were quantified by tandem mass spectrometry in samples from 569 incident colon cancer cases and 569 matched controls. Multivariable logistic regression analyses were used to estimate odds ratios (ORs) for colon cancer risk across quartiles of bile acid concentrations. Results Positive associations were observed between colon cancer risk and plasma levels of seven conjugated bile acid metabolites: the primary bile acids glycocholic acid (ORquartile 4 vs quartile 1= 2.22, 95% confidence interval [CI] = 1.52 to 3.26), taurocholic acid (OR = 1.78, 95% CI = 1.23 to 2.58), glycochenodeoxycholic acid (OR = 1.68, 95% CI = 1.13 to 2.48), taurochenodeoxycholic acid (OR = 1.62, 95% CI = 1.11 to 2.36), and glycohyocholic acid (OR = 1.65, 95% CI = 1.13 to 2.40), and the secondary bile acids glycodeoxycholic acid (OR = 1.68, 95% CI = 1.12 to 2.54) and taurodeoxycholic acid (OR = 1.54, 95% CI = 1.02 to 2.31). By contrast, unconjugated bile acids and tertiary bile acids were not associated with risk. Conclusions This prospective study showed that prediagnostic levels of certain conjugated primary and secondary bile acids were positively associated with risk of colon cancer. Our findings support experimental data to suggest that a high bile acid load is colon cancer promotive.