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Several systematic reviews and meta-analyses have summarized the association between sedentary behavior (SB) and cancer. However, the level of evidence and the potential for risk of bias remains unclear. This umbrella review summarized the current data on SB in relation to cancer incidence and mortality, with a particular emphasis on assessing the risk of bias. We searched PubMed, Web of Science and Cochrane Database for systematic reviews and meta-analyses on the association between SB and cancer incidence and mortality. We also searched for recent observational studies not yet included in existing meta-analyses. We re-calculated summary risk estimates for cancer incidence and mortality using random effects models. We included 14 meta-analyses covering 17 different cancer sites from 77 original studies. We found that high SB levels increase the risk for developing ovarian, endometrial, colon, breast, prostate, and rectal cancers, with relative risks of 1.29 (95% confidence interval (CI) = 1.08–1.56), 1.29 (95% CI = 1.16–1.45), 1.25 (95% CI = 1.16–1.33), 1.08 (95% CI = 1.04–1.11), 1.08 (95% CI = 1.00–1.17), and 1.07 (95% CI = 1.01–1.12), respectively. Also, we found an increased risk of cancer mortality of 1.18 (95% CI = 1.09–1.26). Most associations between SB and specific cancer sites were supported by a “suggestive” level of evidence. High levels of SB are associated with increased risk of several types of cancer and increased cancer mortality risk.

Despite the increasing knowledge about factors shaping the human microbiome, the host genetic factors that modulate the skin-microbiome interactions are still largely understudied. This contrasts with recent efforts to characterize host genes that influence the gut microbiota. Here, we investigated the effect of genetics on skin microbiota across three different skin microenvironments through meta-analyses of genome-wide association studies (GWAS) of two population-based German cohorts. We identified 23 genome-wide significant loci harboring 30 candidate genes involved in innate immune signaling, environmental sensing, cell differentiation, proliferation and fibroblast activity. However, no locus passed the strict threshold for study-wide significance ( P  < 6.3 × 10 −10 for 80 features included in the analysis). Mendelian randomization (MR) analysis indicated the influence of staphylococci on eczema/dermatitis and suggested modulating effects of the microbiota on other skin diseases. Finally, transcriptional profiles of keratinocytes significantly changed after in vitro co - culturing with Staphylococcus epidermidis , chosen as a representative of skin commensals. Seven candidate genes from the GWAS were found overlapping with differential expression in the co-culturing experiments, warranting further research of the skin commensal and host genetic makeup interaction. Microbiome composition is influenced by genetics, although the specific host genetic factors responsible are not well known. Here, the authors performed a genome-wide meta-analysis to discover host genetic effects on skin microbiota and finding potential causal effects of microbiota composition on skin diseases.

Environmental factors such as tobacco smoking may have long-lasting effects on DNA methylation patterns, which might lead to changes in gene expression and in a broader context to the development or progression of various diseases. We conducted an epigenome-wide association study (EWAs) comparing current, former and never smokers from 1793 participants of the population-based KORA F4 panel, with replication in 479 participants from the KORA F3 panel, carried out by the 450K BeadChip with genomic DNA obtained from whole blood. We observed wide-spread differences in the degree of site-specific methylation (with p-values ranging from 9.31E-08 to 2.54E-182) as a function of tobacco smoking in each of the 22 autosomes, with the percent of variance explained by smoking ranging from 1.31 to 41.02. Depending on cessation time and pack-years, methylation levels in former smokers were found to be close to the ones seen in never smokers. In addition, methylation-specific protein binding patterns were observed for cg05575921 within AHRR, which had the highest level of detectable changes in DNA methylation associated with tobacco smoking (-24.40% methylation; p = 2.54E-182), suggesting a regulatory role for gene expression. The results of our study confirm the broad effect of tobacco smoking on the human organism, but also show that quitting tobacco smoking presumably allows regaining the DNA methylation state of never smokers.

Background Sedentary behavior, particularly prolonged sitting, is a significant global public health issue. However, comprehensive population-level temporal trends on sitting time are sparse, hampering effective monitoring and policy development. This study aims to examine temporal trends and correlates of overall and domain-specific sitting time among the adult population in Germany from 2014 to 2023. Methods Data were obtained from five cross-sectional, population-representative telephone surveys conducted in Germany in 2014, 2016, 2018, 2021, and 2023, comprising a total of N = 14,417 adults aged 18 years and older. Participants completed the domain-specific Marshall Sitting Questionnaire, reporting sitting time across five domains: transport, work, television viewing, leisure-time electronic media use, and other leisure activities. Descriptive statistics and linear regression analyses were performed to examine time trends and sociodemographic and lifestyle correlates, with all results presented as mean estimates and 95% confidence intervals. Results Between 2014 and 2023, average overall weekday sitting time increased by 76 minutes per weekday, rising from 457 to 533 minutes. The most pronounced relative increases were observed in work-related (42%) and leisure-time electronic media use (31%). The prevalence of high sitting time (>8 hours/weekday) rose from 42% in 2014 to 55% in 2023. Regression analyses indicated that men (31.8 minutes/weekday, 95% CI: 22.5, 41.1), younger adults (-2.3, 95% CI: -2.5, -2.0), individuals with higher education (57.1, 95% CI: 43.8, 70.4) and income levels (41.7, 95% CI: 25.9, 57.5), and urban residents (21.5, 95% CI: 8.7, 34.2) had significantly longer overall sitting times compared to women, older adults, individuals with lower education and income, and those living in rural areas, respectively. Conclusions Temporal trends from Germany indicate a substantial increase in both overall and domain-specific sitting time between 2014 and 2023, predominantly driven by work-related and screen-based leisure activities. These findings underscore the urgent need for public health strategies aimed at reducing prolonged sitting, particularly in work and leisure contexts. Targeted population-specific and context-sensitive interventions are increasingly needed to mitigate the rise in overall and domain-specific sitting time.

Background Physical activity has been positively related to malignant melanoma. However, that association may be confounded by ultraviolet radiation (UV), a variable closely related to both outdoor physical activity and malignant melanoma. We examined physical activity, grip strength and sedentary behaviour in relation to risk of malignant melanoma, accounting for relevant confounders using data from a prospective cohort study. Methods In 350,512 UK Biobank participants aged 38–73 years at baseline, physical activity was assessed with a modified version of the International Physical Activity Questionnaire Short Form, grip strength was measured with a hand dynamometer, and sedentary behaviour was recorded with three specific questions. Multivariable hazard ratios (HR) and corresponding 95% confidence intervals (CI) were estimated using Cox proportional hazards regression. Results During 7 years of follow-up, 1239 incident malignant melanoma diagnoses were recorded. Physical activity and sedentary behaviour were unrelated to malignant melanoma (HRs 1.01 (95% CI 0.95–1.07) and 1.04 (95% CI 0.97–1.12), respectively), and the initially positive association with grip strength in the basic model (HR 1.23, 95% CI 1.08–1.40) was attenuated after full adjustment (HR 1.10, 95% CI 0.96–1.26). Conclusion Physical activity, grip strength and sedentary behaviour are not associated with malignant melanoma risk.

AimsObservational evidence suggests that physical activity (PA) is inversely and sedentarism positively related with cardiovascular disease risk. We performed a two-sample Mendelian randomization (MR) analysis to examine whether genetically predicted PA and sedentary behavior are related to coronary artery disease, myocardial infarction, and ischemic stroke.Methods and resultsWe used single nucleotide polymorphisms (SNPs) associated with self-reported moderate to vigorous PA (n = 17), accelerometer based PA (n = 7) and accelerometer fraction of accelerations > 425 milli-gravities (n = 7) as well as sedentary behavior (n = 6) in the UK Biobank as instrumental variables in a two sample MR approach to assess whether these exposures are related to coronary artery disease and myocardial infarction in the CARDIoGRAMplusC4D genome-wide association study (GWAS) or ischemic stroke in the MEGASTROKE GWAS. The study population included 42,096 cases of coronary artery disease (99,121 controls), 27,509 cases of myocardial infarction (99,121 controls), and 34,217 cases of ischemic stroke (404,630 controls). We found no associations between genetically predicted self-reported moderate to vigorous PA, accelerometer-based PA or accelerometer fraction of accelerations > 425 milli-gravities as well as sedentary behavior with coronary artery disease, myocardial infarction, and ischemic stroke.ConclusionsThese results do not support a causal relationship between PA and sedentary behavior with risk of coronary artery disease, myocardial infarction, and ischemic stroke. Hence, previous observational studies may have been biased.Graphic abstract

Background Waist circumference and grip strength are each associated with type 2 diabetes (T2D) risk, but their joint associations have been less well studied. Methods We examined the separate and joint associations of waist circumference and grip strength with incident T2D among 483,578 adults aged 40–69 years (55% women) without T2D at baseline (2006–2010) from UK Biobank. Waist circumference was measured by trained staff and categorized using World Health Organization thresholds. Grip strength was assessed using a hydraulic dynamometer and categorized into age- and sex-specific tertiles. Incident T2D was ascertained through linkage to hospital inpatient records until 2022. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression, adjusting for sociodemographic, lifestyle, and clinical covariates. Results During 13.0 years of follow-up (6.3 million person-years), 30,240 participants (6.3%) developed T2D. Compared to individuals with low waist circumference (men: ≤ 94 cm, women: ≤ 80 cm), HRs were 2.11 (95% CI 2.03–2.19) for those with intermediate (men: 95–102 cm, women: 81–88 cm) and 5.48 (95% CI 5.30–5.66) for those with high waist circumference (men: > 102 cm, women: > 88 cm). Compared to individuals with high grip strength, HRs were 1.08 (95% CI 1.05–1.11) for those with intermediate and 1.35 (95% CI 1.32–1.39) for those with low grip strength. Joint analyses showed the highest risk among participants with the combination of high waist circumference and low grip strength (HR 7.68, 95% CI 7.22–8.17) compared to individuals with the combination of low waist circumference and high grip strength. Associations between waist circumference and T2D were stronger in women, whereas associations with grip strength were stronger in men. Both patterns were more pronounced among younger adults. Conclusions Waist circumference and grip strength were separately and jointly associated with T2D risk. The combination of high waist circumference and low grip strength conferred the greatest risk. Joint assessment of waist circumference and grip strength identifies individuals at particularly elevated risk and may inform preventive strategies, though formal evaluation of incremental predictive utility is needed.

Background This prospective interventional study assessed adolescents’ baseline knowledge of the 12 European Code Against Cancer (ECAC) recommendations and evaluated the impact of a school-based multimedia enhanced intervention on knowledge improvement and retention. Methods The intervention comprised six 45-min multimedia lessons promoting knowledge of all 12 ECAC recommendations in German secondary schools. Materials were developed and refined by an interdisciplinary expert panel and underwent pilot testing before implementation. An anonymous single-recall-based, open-ended questionnaire assessed baseline knowledge (t0) and mean knowledge gains immediately post-intervention (t1) and at three months follow-up (t2). Descriptive statistics were computed, with quantitative variables summarized by mean and standard deviation, and qualitative variables by absolute and relative frequencies. Results A total of 923 pupils participated (51.8% female; 39.0% male; 9.2% diverse/undeclared), with 923 completing baseline (t0), 873 post-intervention (t1), and 779 the follow-up assessments (t2). Notable knowledge gaps regarding the ECAC were present at baseline. Mean (M) knowledge scores increased significantly across all three assessment time points with post-intervention scores (t1, M = 7.63 (Standard deviation (SD) = 2.67); p  < 0.0001) significantly higher than at baseline (t0, M = 4.11 (SD = 1.84)). Largest average improvements post intervention (t0-t1) were observed for breastfeeding importance (+ 50%; 1.20% (t0), 51.2% (t1), p  < 0.001), vaccination participation (+ 49.6%; 13.9% (t0), 63.5%(t1), p  < 0.001) and regular physical activity (+ 39.4%, p  < 0.001).The most sustainable recommendation improvements [calculated by (t2-t0)/(t1-t0)] were observed for alcohol abstinence (0.76); healthy dietary pattern (0.72), and physical activity (0.69) respectively. Conclusions: Multimedia enhanced school-based interventions incorporating the ECAC recommendations effectively increase cancer prevention knowledge among adolescents and knowledge retention after three months. While knowledge retention trends indicated a need for reinforcement, our results demonstrate the effectiveness of early, targeted interventions to address baseline knowledge gaps and provide insights that could potentially shape future interventions. Conclusions Multimedia enhanced school-based interventions incorporating the ECAC recommendations effectively increase cancer prevention knowledge among adolescents and knowledge retention after three months. While knowledge retention trends indicated a need for reinforcement, our results demonstrate the effectiveness of early, targeted interventions to address baseline knowledge gaps and provide insights that could potentially shape future interventions. Highlights • Knowledge gaps exist among German adolescents about cancer prevention risk reduction. • School-based digital interventions significantly reduce knowledge gaps. • Greatest knowledge retention after 3 months was for alcohol abstinence, having a healthy diet and increasing physical activity. • Knowledge retention trend shows a need for reinforcement to obtain sustained results

Interleukin 6 (IL-6) is considered to play a role in the dysbiotic host response in the development of periodontitis. While the inhibition of the IL-6 receptor using monoclonal antibodies is a well-established therapy for some diseases, so far, its potential benefit in patients with periodontitis has not been examined. We tested the association of genetically proxied downregulation of IL-6 signaling with periodontitis to explore whether downregulation of IL-6 signaling could represent a viable treatment target for periodontitis. As proxies for IL-6 signaling downregulation, we selected 52 genetic variants in close vicinity of the gene encoding IL-6 receptor that were associated with lower circulating C-reactive protein (CRP) levels in a genome-wide association study (GWAS) of 575 531 participants of European ancestry from the UK Biobank and the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. Associations with periodontitis were tested with inverse-variance weighted Mendelian randomization in a study of 17 353 cases and 28 210 controls of European descent in the Gene-Lifestyle Interactions in Dental Endpoints (GLIDE) consortium. In addition, the effect of CRP reduction independent of the IL-6 pathway was assessed. Genetically proxied downregulation of IL-6 signaling was associated with lower odds of periodontitis (odds ratio (OR) = 0.81 per 1-unit decrement in log-CRP levels; 95% confidence interval (CI): [0.66;0.99]; P = 0.0497). Genetically proxied reduction of CRP independent of the IL-6 pathway had a similar effect (OR = 0.81; 95% CI: [0.68; 0.98]; P = 0.0296). In conclusion, genetically proxied downregulation of IL-6 signaling was associated with lower odds of periodontitis and CRP might be a causal target for the effect of IL-6 on the risk of periodontitis.