Gender differences in lung cancer risk by smoking: a multicentre case-control study in Germany and Italy

Several studies in the past have shown appreciably higher lung cancer risk estimates associated with smoking exposure among men than among women, while more recent studies in the USA report just the opposite. To evaluate this topic in a European population we conducted a case-control study of lung cancer in three German and three Italian centres. Personal interviews and standardized questionnaires were used to obtain detailed life-long smoking and occupational histories from 3723 male and 900 female cases and 4075 male and 1094 female controls. Lung cancer risk comparing ever-smokers with never-smokers was higher among men (odds ratios (OR) adjusted for age and centre = 16.1, 95% confidence interval (CI) 12.8-20.3) than among women (OR = 4.2, CI 3.5-5.1). Because the smoking habits of women were different from men, we conducted more detailed analyses using comparable levels of smoking exposure. After restriction to smokers and adjustment for other smoking variables, risk estimates did not differ appreciably between genders. The analysis of duration of smoking (0-19, 20-39, 40+ years) adjusted for cigarette consumption and time since quitting smoking revealed similar risk estimates in men (OR = 1.0, 3.3 [CI 2.6-4.2], 4.1 [CI 3.1-5.6]) and women (OR = 1.0, 2.7 [CI 1.7-4.1], 3.3 [CI 1.9-5.8]). The same was true of the analysis of average or cumulative smoking consumption, and also of analyses stratified by different histological types. We conclude that for comparable exposure to tobacco smoke, the risk of lung cancer is comparable in women and men

Statistical analysis in the German National Cohort (NAKO) - specific aspects and general recommendations

The German National Cohort (NAKO) is an ongoing, prospective multicenter cohort study, which started recruitment in 2014 and includes more than 205,000 women and men aged 19-74 years. The study data will be available to the global research community for analyses. Although the ultimate decision about the analytic methods will be made by the respective investigator, in this paper we provide the basis for a harmonized approach to the statistical analyses in the NAKO. We discuss specific aspects of the study (e.g., data collection, weighting to account for the sampling design), but also give general recommendations which may apply to other large cohort studies as well

Analysis of volume and topography of adipose tissue in the trunk: Results of MRI of 11,141 participants in the German National Cohort

This research addresses the assessment of adipose tissue (AT) and spatial distribution of visceral (VAT) and subcutaneous fat (SAT) in the trunk from standardized magnetic resonance imaging at 3 T, thereby demonstrating the feasibility of deep learning (DL)-based image segmentation in a large population-based cohort in Germany (five sites). Volume and distribution of AT play an essential role in the pathogenesis of insulin resistance, a risk factor of developing metabolic/cardiovascular diseases. Cross-validated training of the DL-segmentation model led to a mean Dice similarity coefficient of >0.94, corresponding to a mean absolute volume deviation of about 22 ml. SAT is significantly increased in women compared to men, whereas VAT is increased in males. Spatial distribution shows age- and body mass index-related displacements. DL-based image segmentation provides robust and fast quantification of AT (≈15 s per dataset versus 3 to 4 hours for manual processing) and assessment of its spatial distribution from magnetic resonance images in large cohort studies

Occupation and SARS-CoV-2 infection risk among 108 960 workers during the first pandemic wave in Germany

OBJECTIVE: The aim of this study was to identify the occupational risk for a SARS-CoV-2 infection in a nationwide sample of German workers during the first wave of the COVID-19 pandemic (1 February-31 August 2020). METHODS: We used the data of 108 960 workers who participated in a COVID follow-up survey of the German National Cohort (NAKO). Occupational characteristics were derived from the German Classification of Occupations 2010 (Klassifikation der Berufe 2010). PCR-confirmed SARS-CoV-2 infections were assessed from self-reports. Incidence rates (IR) and incidence rate ratios (IRR) were estimated using robust Poisson regression, adjusted for person-time at risk, age, sex, migration background, study center, working hours, and employment relationship. RESULTS: The IR was 3.7 infections per 1000 workers [95% confidence interval (CI) 3.3-4.1]. IR differed by occupational sector, with the highest rates observed in personal (IR 4.8, 95% CI 4.0-5.6) and business administration (IR 3.4, 95% CI 2.8-3.9) services and the lowest rates in occupations related to the production of goods (IR 2.0, 95% CI 1.5-2.6). Infections were more frequent among essential workers compared with workers in non-essential occupations (IRR 1.95, 95% CI 1.59-2.40) and among highly skilled compared with skilled professions (IRR 1.36, 95% CI 1.07-1.72). CONCLUSIONS: The results emphasize higher infection risks in essential occupations and personal-related services, especially in the healthcare sector. Additionally, we found evidence that infections were more common in higher occupational status positions at the beginning of the pandemic

Grip strength values and cut-off points based on over 200,000 adults of the German National Cohort - a comparison to the EWGSOP2 cut-off points

BACKGROUND: The European Working Group on Sarcopenia in Older People (EWGSOP) updated in 2018 the cut-off points for low grip strength to assess sarcopenia based on pooled data from 12 British studies. OBJECTIVE: Comparison of the EWGSOP2 cut-off points for low grip strength to those derived from a large German sample. METHODS: We assessed the grip strength distribution across age and derived low grip strength cut-off points for men and women (peak mean -2.5 × SD) based on 200,389 German National Cohort (NAKO) participants aged 19-75 years. In 1,012 Cooperative Health Research in the Region of Augsburg (KORA)-Age participants aged 65-93 years, we calculated the age-standardised prevalence of low grip strength and time-dependent sensitivity and specificity for all-cause mortality. RESULTS: Grip strength increased in the third and fourth decade of life and declined afterwards. Calculated cut-off points for low grip strength were 29 kg for men and 18 kg for women. In KORA-Age, the age-standardised prevalence of low grip strength was 1.5× higher for NAKO-derived (17.7%) compared to EWGSOP2 (11.7%) cut-off points. NAKO-derived cut-off points yielded a higher sensitivity and lower specificity for all-cause mortality. CONCLUSIONS: Cut-off points for low grip strength from German population-based data were 2 kg higher than the EWGSOP2 cut-off points. Higher cut-off points increase the sensitivity, thereby suggesting an intervention for more patients at risk, while other individuals might receive additional diagnostics/treatment without the urgent need. Research on the effectiveness of intervention in patients with low grip strength defined by different cut-off points is needed

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

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

Exposure to welding fumes, hexavalent chromium, or nickel and risk of lung cancer.

To investigate the risk of lung cancer after exposure to welding fumes, hexavalent chromium (Cr(VI)), and nickel, we analyzed 3,418 lung cancer cases and 3,488 controls among men from 2 German case-control studies (1988-1996). We developed a welding-process exposure matrix from measurements of these agents, and this was linked with welding histories from a job-specific questionnaire to calculate cumulative exposure variables. Logistic regression models were fitted to estimate odds ratios with confidence intervals conditional on study, and they adjusted for age, smoking, and working in other at-risk occupations. Additionally, we mutually adjusted for the other exposure variables under study. Overall, 800 cases and 645 controls ever worked as regular or occasional welders. Odds ratios for lung cancer with high exposure were 1.55 (95% confidence interval (CI): 1.17, 2.05; median, 1.8 mg/m(3) x years) for welding fumes, 1.85 (95% CI: 1.35, 2.54; median, 1.4 mu g/m(3) x years) for Cr(VI), and 1.60 (95% CI: 1.21, 2.12; median, 9 mu g/m(3) x years) for nickel. Risk estimates increased with increasing cumulative exposure to welding fumes and with increasing exposure duration for Cr(VI) and nickel. Our results showed that welding fumes, Cr(VI), and nickel might contribute independently to the excess lung cancer risk associated with welding. However, quantitative exposure assessment remains challenging

Night work, chronotype and cortisol at awakening in female hospital employees.

To examine the effect of night shift on salivary cortisol at awakening (C1), 30 min later (C2), and on the cortisol awakening response (CAR, the difference between C2 and C1). We compared shift and non-shift workers with a focus on the impact of worker chronotype. Our study included 66 shift-working females (mean age = 37.3 years, SD = 10.2) and 21 non-shift working females (mean age = 47.0 years, SD = 8.9). The shift workers collected their saliva samples at C1 and C2 on each two consecutive day shifts and night shifts. Non-shift workers collected their samples on two consecutive day shifts. We applied linear mixed-effects models (LMM) to determine the effect of night shift on CAR and log-transformed C1 and C2 levels. LMMs were stratified by chronotype group. Compared to non-shift workers, shift workers before day shifts (i.e. after night sleep) showed lower cortisol at C1 (exp [Formula: see text]=0.58, 95% CI 0.42, 0.81) but not at C2. In shift workers, the CARs after night shifts (i.e. after day sleep) were lower compared to CARs before day shifts ([Formula: see text]= - 11.07, 95% CI - 15.64, - 6.50). This effect was most pronounced in early chronotypes (early: [Formula: see text]= - 16.61, 95% CI - 27.87, - 5.35; intermediate: [Formula: see text]= - 11.82, 95% CI - 18.35, - 5.29; late: [Formula: see text]= - 6.27, 95% CI - 14.28, 1.74). Chronotype did not modify the association between night shift and CAR. In our population of shift workers, there was a mismatch between time of waking up and their natural cortisol peak at waking up (CAR) both during day and night shift duties