Consumption of ultra-processed foods and risk of multimorbidity of cancer and cardiometabolic diseases: a multinational cohort study.

Background: It is currently unknown whether ultra-processed foods (UPFs) consumption is associated with a higher incidence of multimorbidity. We examined the relationship of total and subgroup consumption of UPFs with the risk of multimorbidity defined as the co-occurrence of at least two chronic diseases in an individual among first cancer at any site, cardiovascular disease, and type 2 diabetes. Methods: This was a prospective cohort study including 266,666 participants (60% women) free of cancer, cardiovascular disease, and type 2 diabetes at recruitment from seven European countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Foods and drinks consumed over the previous 12 months were assessed at baseline by food-frequency questionnaires and classified according to their degree of processing using Nova classification. We used multistate modelling based on Cox regression to estimate cause-specific hazard ratios (HR) and their 95% confidence intervals (CI) for associations of total and subgroups of UPFs with the risk of multimorbidity of cancer and cardiometabolic diseases. Findings: After a median of 11.2 years of follow-up, 4461 participants (39% women) developed multimorbidity of cancer and cardiometabolic diseases. Higher UPF consumption (per 1 standard deviation increment, ∼260 g/day without alcoholic drinks) was associated with an increased risk of multimorbidity of cancer and cardiometabolic diseases (HR: 1.09, 95% CI: 1.05, 1.12). Among UPF subgroups, associations were most notable for animal-based products (HR: 1.09, 95% CI: 1.05, 1.12), and artificially and sugar-sweetened beverages (HR: 1.09, 95% CI: 1.06, 1.12). Other subgroups such as ultra-processed breads and cereals (HR: 0.97, 95% CI: 0.94, 1.00) or plant-based alternatives (HR: 0.97, 95% CI: 0.91, 1.02) were not associated with risk. Interpretation: Our findings suggest that higher consumption of UPFs increases the risk of cancer and cardiometabolic multimorbidity. Funding: Austrian Academy of Sciences, Fondation de France, Cancer Research UK, World Cancer Research Fund International, and the Institut National du Cancer.

Health behavior of Austrian tertiary students focusing on diet type linked to sports and exercise-first glimpse of results from the "sustainably healthy-from science 2 high school and university" study.

Background: There is a strong association between lifestyle behavior and health status. While young adulthood is a critical period for adopting and stabilizing lifelong healthy behavior, university life is independently associated with psychological stressors that may further affect health and well-being. Objective: The present multidisciplinary study aimed to examine the health behavior of Austrian college and university students, differentiated based on diet types (vegan, vegetarian, and omnivorous) and physical activity (PA) habits. Methods: Following a cross-sectional study design, a total number of 6,148 students (65.3% females; 66.1% bachelor students, 67.0% from urban areas; mean age: 24.8 years) from 52 Austrian college/universities participated in an online survey and provided data on sociodemographic characteristics, dietary patterns, PA habits, and other lifestyle behavior characteristics, including alcohol intake and smoking. Results: Across the total sample, 74.0% had a normal weight (BMI = 18.5-25.0 kg/m2), while the prevalence of overweight/obesity (BMI ≥ 30.0 kg/m2) was lower in females than males and more in rural than urban students (p < 0.01). The general prevalence of vegetarian and vegan diets was 22.8 and 6.0%, respectively, with a predominance of females, graduates, and urban students compared to their peers (p < 0.01). The majority of students (79.3%) had a regular engagement in sport/exercise, with a predominance of vegetarian or vegan students compared to omnivores (p < 0.01). Vegans and vegetarians had a lower alcohol intake (p < 0.01) but no differences in smoking habits (p > 0.05) compared to omnivores. Students engaging in sport/exercise had a lower smoking rate and higher intake of fruits, vegetables, and fluids compared to inactive students (p < 0.01). Conclusion: The present findings suggest that diet type and PA habits of college/university students have an impact on other health behaviors, highlighting the interconnected nature of lifestyle habits and health behavior.

A glimpse of academic staff health behavior on diet type and physical activity at Austrian universities: first findings from the "Sustainably Healthy - From Science 2 Highschool & University" study.

Background: The association between lifestyle and health status highlights the importance of assessing health-related behavior in different populations. This multidisciplinary study aimed to examine the health behavior of academic staff of Austrian colleges and universities, with a specific focus on diet types (vegan, vegetarian, omnivorous) and physical activity (PA) reports. Methods: Following a cross-sectional study design incorporating an online survey, a sample of 1,041 academics from 52 institutes (mean age: 46.4 years) provided data on sociodemographic characteristics, dietary patterns, PA behavior, and other lifestyle behaviors (smoking, alcohol intake, etc.). Results: The prevalence of vegetarian and vegan diets was 13.2 and 2.0%, respectively, and 33.2% of participants had excess body weight (BMI ≥ 25). The majority of participants (88.5%) reported regularly engaging in leisure-time PA, but 18.6% were active members of sports clubs. No difference between females and males was observed in diet type and the type of sport participation (p > 0.05). Participants with a mixed diet had a higher BMI than vegetarians and vegans (p < 0.05). Leisure-time PA participation was associated with more frequent fruit and vegetable intake (p < 0.05). The prevalence of smoking and alcohol intake was 13.1 and 73.5%, respectively, without any difference between dietary or sports participation subgroups (p > 0.05). Conclusion: The present study provides an overview of the social trends in vegan and vegetarian diets linked to health behaviors in tertiary educational settings. Findings can be used by health scientists, decision-makers, and multipliers in health and education to improve public health.

Association between salt intake and gastric atrophy by Helicobacter pylori infection: first results from the Epidemiological Investigation of Gastric Malignancy (ENIGMA).

PURPOSE: Gastric atrophy (GA), usually linked to chronic infection with Helicobacter pylori (H. pylori), may over time evolve into gastric malignancy. Besides H. pylori, high salt intake may play a role in GA development. This study evaluates cross sectionally the association between salt intake and GA in Chilean adults. METHODS: Population-based samples were recruited from two sites, Antofagasta and Valdivia, partaking in the Epidemiological Investigation of Gastric Malignancies. At recruitment, participants answered questionnaires and provided biospecimens. Salt intake (g/day) was estimated from casual spot urine samples using the Tanaka equation. GA was determined by serum pepsinogen levels. Only participants ≥ 40 to 70 years of age were considered in this analysis, n = 565. For the association between salt intake (as sex-specific quartiles) and GA, odds ratios (ORs) and the corresponding 95% confidence intervals (CI) were estimated through multivariable logistic regression. RESULTS: In women, the multivariable-adjusted OR for GA comparing quartile 4 of the estimated salt intake (12.8 g/day) to quartile 1 (6.6 g/day) was 1.18 (95% CI 0.52-2.68, P-trend = 0.87). The corresponding OR in men was 0.49 (95% CI 0.19-1.27, P-trend = 0.17) with salt intakes of 12.8 g/day and 7.1 g/day for quartiles 4 and 1, respectively. CONCLUSION: There was little evidence for an association between salt intake estimated from spot urine and GA risk in our cross-sectional analysis of middle aged and older adults in Chile. Reverse causation bias cannot be ruled out and the sample size was limited to provide more precise estimates.

Study Protocol of "Sustainably Healthy-From Science 2 Highschool & University"-Prevalence of Mixed, Vegetarian, and Vegan Diets Linked to Sports & Exercise among Austrian Tertiary Students and Lecturers/Academic Staff.

Healthy lifestyle is the major indicator of individual and public health especially in target populations (e.g., during emerging adulthood). Evidence indicates that unhealthy lifestyle behaviors are strongly associated with the increasing prevalence of chronic diseases. The dual approach of sustainable health (i.e., physical exercise tied to a healthy diet) is an effective lifestyle strategy to control and manage health-related disorders, including overweight/obesity. Based on the evidence on plant-based diets regarding health and considering the growing prevalence of vegans and vegetarians worldwide, limited data exist on the health-related behaviors of those who follow plant-based vs. mixed diets in young adulthood. This multidisciplinary study is the first to examine the association between diet type (mixed, vegetarian, and vegan diets) and various health-related behaviors (primarily physical activity, sport, & exercise) among college/university students and lecturers/academic staff in Austria nationwide. Following a cross-sectional study design and using online questionnaires, 4510 tertiary students and 1043 lecturers/academic staff provided data on sociodemographic characteristics, dietary patterns, physical exercise habits, and other lifestyle behaviors (sleep, alcohol intake, smoking, etc.) along with information on health status and quality of life. While the data will be analyzed based on differentiated sociodemographic and health-related categories, the influence of the COVID-19 pandemic on lifestyle behaviors will also be evaluated. As a study protocol, this article represents comprehensive details of the design, purposes, and associated analytical measures of the present study within the tertiary educational context.

Handgrip Strength Values Depend on Tumor Entity and Predict 180-Day Mortality in Malnourished Cancer Patients.

BACKGROUND: Cancer-related malnutrition is a prevalent condition associated with a loss of muscle mass and impaired functional status, leading to immunodeficiency, impaired quality of life and adverse clinical outcomes. Handgrip strength (HGS) is a practical measure to assess muscle strength in individual patients during clinical practice. However, HGS reference values refer to populations of healthy people, and population-specific values, such as those in the population of cancer patients, still need to be defined. METHODS: Within a secondary analysis of a previous randomized controlled nutritional trial focusing on hospitalized cancer patients at risk for malnutrition, we investigated sex-specific HGS values stratified by age and tumor entity. Additionally, we examined the association between HGS and 180-day all-cause mortality. RESULTS: We included data from 628 cancer patients, which were collected from eight hospitals in Switzerland. Depending on the age of patients, HGS varied among female patients from 7 kg to 26 kg and among male patients from 20.5 kg to 44 kg. An incremental decrease in handgrip strength by 10 kg resulted in a 50% increase in 180-day all-cause mortality (odds ratio 1.52 (95%CI 1.19 to 1.94), p = 0.001). CONCLUSION: Our data provide evidence of the prognostic implications of HGS measurement in cancer patients and validate the prognostic value of handgrip strength in regard to long-term mortality. In addition, our results provide expected HGS values in the population of hospitalized malnourished cancer patients, which may allow better interpretation of values in individual patients.

Factors Associated with (Exclusive) Breastfeeding Duration-Results of the SUKIE-Study.

The WHO European Region has the lowest exclusive breastfeeding (EBF) rates at 6 months in the world. In Austria, 55.5% of infants are EBF at the age of one week, although breastfeeding initiation is 97.5%. The study was conducted in 2019/2020 and considered 1214 mothers of legal age, who received four online questionnaires during their child's first year of life. The influence of different variables on total/exclusive breastfeeding duration were analysed by using a Cox model (Extension of the Cox Proportional Hazards Model) with time-dependent covariates. Multivariate analyses showed a significant influence of maternal BMI, lifestyle factors, such as smoking, and breastfeeding support on total breastfeeding duration. Remarkable differences in the median duration of any breastfeeding were found for breastfeeding support, where mothers breastfed twice as long. Support came primarily from hospital staff, the midwife and the partner. A higher monthly household net income, delivery in a baby-friendly certified hospital (BFH) and breastfeeding support were associated with a longer EBF duration. Obese mothers started feeding infant formula earlier and had a higher risk of early weaning. The results offer valuable insights into the importance of breastfeeding-friendly structures such as BFHs, a focus on breastfeeding aftercare and support of the mother to promote and protect breastfeeding.

Nutritional supplementation alters associations between one-carbon metabolites and cardiometabolic risk profiles in older adults: a secondary analysis of the Vienna Active Ageing Study.

PURPOSE: Cardiovascular diseases and cognitive decline, predominant in ageing populations, share common features of dysregulated one-carbon (1C) and cardiometabolic homeostasis. However, few studies have addressed the impact of multifaceted lifestyle interventions in older adults that combine both nutritional supplementation and resistance training on the co-regulation of 1C metabolites and cardiometabolic markers. METHODS: 95 institutionalised older adults (83 ± 6 years, 88.4% female) were randomised to receive resistance training with or without nutritional supplementation (Fortifit), or cognitive training (control for socialisation) for 6 months. Fasting plasma 1C metabolite concentrations, analysed by liquid chromatography coupled with mass spectrometry, and cardiometabolic parameters were measured at baseline and the 3- and 6-month follow-ups. RESULTS: Regardless of the intervention group, choline was elevated after 3 months, while cysteine and methionine remained elevated after 6 months (mixed model time effects, p < 0.05). Elevated dimethylglycine and lower betaine concentrations were correlated with an unfavourable cardiometabolic profile at baseline (spearman correlations, p < 0.05). However, increasing choline and dimethylglycine concentrations were associated with improvements in lipid metabolism in those receiving supplementation (regression model interaction, p < 0.05). CONCLUSION: Choline metabolites, including choline, betaine and dimethylglycine, were central to the co-regulation of 1C metabolism and cardiometabolic health in older adults. Metabolites that indicate upregulated betaine-dependent homocysteine remethylation were elevated in those with the greatest cardiometabolic risk at baseline, but associated with improvements in lipid parameters following resistance training with nutritional supplementation. The relevance of how 1C metabolite status might be optimised to protect against cardiometabolic dysregulation requires further attention.

"Micronuclei and Disease" special issue: Aims, scope, and synthesis of outcomes.

The purpose of the "Micronuclei and Disease" special issue (SI) is to: (i) Determine the level of evidence for association of micronuclei (MN), a biomarker of numerical and structural chromosomal aberrations, with risk of specific diseases in humans; (ii) Define plausible mechanisms that explain association of MN with each disease; (iii) Identify knowledge gaps and research needed to translate MN assays into clinical practice. The "MN and Disease" SI includes 14 papers. The first is a review of mechanisms of MN formation and their consequences in humans. 11 papers are systematic reviews and/or meta-analyses of the association of MN with reproduction, child health, inflammation, auto-immune disease, glycation, metabolic diseases, chronic kidney disease, cardiovascular disease, eleven common cancers, ageing and frailty. The penultimate paper focuses on effect of interventions on MN frequency in the elderly. A road map for translation of MN data into clinical practice is the topic of the final paper. The majority of reviewed studies were case-control studies in which the ratio of mean MN frequency in disease cases relative to controls, i.e. the mean ratio (MR), was calculated. The mean of these MR values, estimated by meta-analyses, for lymphocyte and buccal cell MN in non-cancer diseases were 2.3 and 3.6 respectively, and for cancers they were 1.7 and 2.6 respectively. The highest MR values were observed in studies of cancer cases in which MN were measured in the same tissue as the tumour (MR = 4.9-10.8). This special issue is an important milestone in the evidence supporting MN as a reliable genomic biomarker of developmental and degenerative disease risk. These advances, together with results from prospective cohort studies, are helping to identify diseases in which MN assays can be practically employed in the clinical setting to better identify high risk patients and to prioritise them for preventive therapy.

Gilbert's Syndrome and the Gut Microbiota - Insights From the Case-Control BILIHEALTH Study.

The heme catabolite bilirubin has anti-inflammatory, anti-oxidative and anti-mutagenic effects and its relation to colorectal cancer (CRC) risk is currently under evaluation. Although the main metabolic steps of bilirubin metabolism, including the formation of stercobilin and urobilin, take place in the human gastrointestinal tract, potential interactions with the human gut microbiota are unexplored. This study investigated, whether gut microbiota composition is altered in Gilbert's Syndrome (GS), a mild form of chronically elevated serum unconjugated bilirubin (UCB) compared to matched controls. Potential differences in the incidence of CRC-associated bacterial species in GS were also assessed. To this end, a secondary investigation of the BILIHEALTH study was performed, assessing 45 adults with elevated UCB levels (GS) against 45 age- and sex-matched controls (C). Fecal microbiota analysis was performed using 16S rRNA gene sequencing. No association between mildly increased UCB and the composition of the gut microbiota in this healthy cohort was found. The alpha and beta diversity did not differ between C and GS and both groups showed a typical representation of the known dominant phyla. Furthermore, no difference in abundance of Firmicutes and Proteobacteria, which have been associated with the mucosa of CRC patients were observed between the groups. A sequence related to the Christensenella minuta strain YIT 12065 was identified with a weak association value of 0.521 as an indicator species in the GS group. This strain has been previously associated with a lower body mass index, which is typical for the GS phenotype. Overall, sex was the only driver for an identifiable difference in the study groups, as demonstrated by a greater bacterial diversity in women. After adjusting for confounding factors and multiple testing, we can conclude that the GS phenotype does not affect the composition of the human gut microbiota in this generally healthy study group.

Consumption of ultra-processed foods associated with weight gain and obesity in adults: A multi-national cohort study.

BACKGROUND: There is a worldwide shift towards increased consumption of ultra-processed foods (UPF) with concurrent rising prevalence of obesity. We examined the relationship between the consumption of UPF and weight gain and risk of obesity. METHODS: This prospective cohort included 348 748 men and women aged 25-70 years. Participants were recruited between 1992 and 2000 from 9 European countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Two body weight measures were available, at baseline and after a median follow-up time of 5 years. Foods and drinks were assessed at baseline by dietary questionnaires and classified according to their degree of processing using NOVA classification. Multilevel mixed linear regression was used to estimate the association between UPF consumption and body weight change (kg/5 years). To estimate the relative risk of becoming overweight or obese after 5 years we used Poisson regression stratified according to baseline body mass index (BMI). RESULTS: After multivariable adjustment, higher UPF consumption (per 1 SD increment) was positively associated with weight gain (0·12 kg/5 years, 95% CI 0·09 to 0·15). Comparing highest vs. lowest quintile of UPF consumption was associated with a 15% greater risk (95% CI 1·11, 1·19) of becoming overweight or obese in normal weight participants, and with a 16% greater risk (95% CI 1·09, 1·23) of becoming obese in participants who were overweight at baseline. CONCLUSIONS: These results are supportive of public health campaigns to substitute UPF for less processed alternatives for obesity prevention and weight management.

Associations between Prediagnostic Circulating Bilirubin Levels and Risk of Gastrointestinal Cancers in the UK Biobank.

We investigated associations between serum levels of bilirubin, an endogenous antioxidant, and gastrointestinal cancer risk. In the UK Biobank, prediagnostic serum levels of total bilirubin were measured in blood samples collected from 440,948 participants. In multivariable-adjusted Cox proportional hazard regression, we estimated hazard ratios (HR) and 95% confidence intervals (CI) for associations between bilirubin levels and gastrointestinal cancer risk (colorectum, esophagus, stomach, mouth, pancreas, and liver). After a median follow-up of 7.1 years (interquartile range: 1.4), 5033 incident gastrointestinal cancer cases were recorded. In multivariable-adjusted models, bilirubin levels were negatively associated with risk of esophageal adenocarcinoma (EAC, HR per 1-SD increment in log-total bilirubin levels 0.72, 95%CI 0.56-0.92, p = 0.01). Weak and less robust negative associations were observed for colorectal cancer (CRC, HR per 1-SD increment in log-total bilirubin levels 0.95, 95%CI 0.88-1.02, p = 0.14). Bilirubin levels were positively associated with risk of hepatocellular carcinoma (HCC, HR per 1-SD increment in log-total bilirubin levels 2.07, 95%CI 1.15-3.73, p = 0.02) and intrahepatic bile duct (IBD) cancer (HR per 1-SD increment 1.67, 95%CI 1.07-2.62, p = 0.03). We found no associations with risks of stomach, oral, and pancreatic cancers. Prediagnostic serum levels of bilirubin were negatively associated with risk of EAC and positively associated with HCC and IBD cancer. Further studies are warranted to replicate our findings for specific GI cancers.

Impact of dietary and lifestyle interventions in elderly or people diagnosed with diabetes, metabolic disorders, cardiovascular disease, cancer and micronutrient deficiency on micronuclei frequency - A systematic review and meta-analysis.

Chronic diseases such as cardiovascular diseases, type 2 diabetes or cancer are the global leading cause of mortality. Lifestyle interventions are most effective in reducing metabolic risk factors, disease progression or even side effects of a disease. They are also contributing to decelerate the aging process. Genome instability is very often associated with aging or the above-mentioned diseases, and triggered by inflammation and oxidative stress. An established method to measure chromosomal damage is the cytokinesis block micronucleus (CBMN) cytome assay. The aim of this review and meta-analysis is to collect and analyse the current literature regarding the effects of a lifestyle based (dietary) intervention on changes of micronuclei (MNi), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) in elderly subjects or people diagnosed with diabetes, metabolic disorders, cardiovascular disease, cancer or micronutrient deficiency. Although the main important diseases were considered as well as the large topic of aging, the number and methodological quality in terms of samples size, duration and rationale of the intervention or an inclusion of a control group of available intervention studies with these backgrounds was low. Most of the studies used antioxidant vitamins or folate, few investigated the whole diet. Only one study showed a physical activity intervention approach. The interventions did not lead to decreased genomic marker despite a few cancer related studies, where particularly MN frequency in mucosa lesions and leukoplakia was reduced by green tea and antioxidants. The performed meta-analysis of the available RCTs did not show a significant reduction of MNi, NBUDs or NPBs of most of the interventions performed, except for green tea. Data show in general a lack of an appropriate number of sound lifestyle based intervention studies linking cytogenetic damage and chronic diseases.

Responsiveness of one-carbon metabolites to a high-protein diet in older men: Results from a 10-wk randomized controlled trial.

OBJECTIVES: Dietary strategies to promote successful aging are divergent. Higher-protein diets are recommended to preserve skeletal muscle mass and physical function. Conversely, increased B-vitamin intake, supporting one-carbon (1C) metabolism, reduces the risk of cognitive decline and cardiovascular disease. On the hypothesis that higher protein intake through animal-based sources will benefit 1C regulation by the supply of B vitamins (folate, riboflavin, and vitamins B6 and B12) and methyl donors (choline) despite higher methionine intake, this study explored the effect of a higher-protein diet on 1C metabolite status in older men compared to current protein recommendations. METHODS: Older men (age, 74 ± 3 y) were randomized to receive a diet for 10 wk containing either the recommended dietary allowance (RDA) of protein (0.8 g/kg body weight/d, n = 14), or double that amount (2RDA, n = 15), with differences in protein accounted for by modifying carbohydrate intake. Intervention diets were matched to each individual's energy requirements based on the Harris-Benedict equation and adjusted fortnightly as required depending on physical activity and satiety. Fasting plasma 1C metabolite concentrations were quantified by liquid chromatography coupled with mass spectrometry at baseline and after 10 wk of intervention. RESULTS: Plasma homocysteine concentrations were reduced from baseline to follow-up with both diets. Changes in metabolite ratios reflective of betaine-dependent homocysteine remethylation were specific to the RDA diet, with an increase in the betaine-to-choline ratio and a decrease in the dimethylglycine-to-betaine ratio. Comparatively, increasing folate intake was positively associated with a change in choline concentration and inversely with the betaine-to-choline ratio for the 2RDA group. CONCLUSIONS: Adding to the known benefits of higher protein intake in older people, this study supports a reduction of homocysteine with increased consumption of animal-based protein, although the health effects of differential response of choline metabolites to a higher-protein diet remain uncertain.

Dietary intake of advanced glycation endproducts and risk of hepatobiliary cancers: A multinational cohort study.

Advanced glycation endproducts (AGEs) may contribute to liver carcinogenesis because of their proinflammatory and prooxidative properties. Diet is a major source of AGEs, but there is sparse human evidence on the role of AGEs intake in liver cancer etiology. We examined the association between dietary AGEs and the risk of hepatobiliary cancers in the European Prospective Investigation into Cancer and Nutrition prospective cohort (n = 450 111). Dietary intake of three AGEs, Nε -[carboxymethyl]lysine (CML), Nε -[1-carboxyethyl]lysine (CEL) and Nδ -[5-hydro-5-methyl-4-imidazolon-2-yl]-ornithine (MG-H1), was estimated using country-specific dietary questionnaires linked to an AGEs database. Cause-specific hazard ratios (HR) and their 95% confidence intervals (CI) for associations between dietary AGEs and risk of hepatocellular carcinoma (HCC), gallbladder and biliary tract cancers were estimated using multivariable Cox proportional hazard regression. After a median follow-up time of 14.9 years, 255 cases of HCC, 100 cases of gallbladder cancer and 173 biliary tract cancers were ascertained. Higher intakes of dietary AGEs were inversely associated with the risk of HCC (per 1 SD increment, HR-CML  = 0.87, 95% CI: 0.76-0.99, HR-CEL  = 0.84, 95% CI: 0.74-0.96 and HR-MH-G1  = 0.84, 95% CI: 0.74-0.97). In contrast, positive associations were observed with risk of gallbladder cancer (per 1 SD, HR-CML  = 1.28, 95% CI: 1.05-1.56, HR-CEL  = 1.17; 95% CI: 0.96-1.40, HR-MH-G1  = 1.27, 95% CI: 1.06-1.54). No associations were observed for cancers of the intra and extrahepatic bile ducts. Our findings suggest that higher intakes of dietary AGEs are inversely associated with the risk of HCC and positively associated with the risk of gallbladder cancer.

Genetically Raised Circulating Bilirubin Levels and Risk of Ten Cancers: A Mendelian Randomization Study.

Bilirubin, an endogenous antioxidant, may play a protective role in cancer development. We applied two-sample Mendelian randomization to investigate whether genetically raised bilirubin levels are causally associated with the risk of ten cancers (pancreas, kidney, endometrium, ovary, breast, prostate, lung, Hodgkin's lymphoma, melanoma, and neuroblastoma). The number of cases and their matched controls of European descent ranged from 122,977 and 105,974 for breast cancer to 1200 and 6417 for Hodgkin's lymphoma, respectively. A total of 115 single-nucleotide polymorphisms (SNPs) associated (p < 5 × 10-8) with circulating total bilirubin, extracted from a genome-wide association study in the UK Biobank, were used as instrumental variables. One SNP (rs6431625) in the promoter region of the uridine-diphosphoglucuronate glucuronosyltransferase1A1 (UGT1A1) gene explained 16.9% and the remaining 114 SNPs (non-UGT1A1 SNPs) explained 3.1% of phenotypic variance in circulating bilirubin levels. A one-standarddeviation increment in circulating bilirubin (≈ 4.4 µmol/L), predicted by non-UGT1A1 SNPs, was inversely associated with risk of squamous cell lung cancer and Hodgkin's lymphoma (odds ratio (OR) 0.85, 95% confidence interval (CI) 0.73-0.99, P 0.04 and OR 0.64, 95% CI 0.42-0.99, p 0.04, respectively), which was confirmed after removing potential pleiotropic SNPs. In contrast, a positive association was observed with the risk of breast cancer after removing potential pleiotropic SNPs (OR 1.12, 95% CI 1.04-1.20, p 0.002). There was little evidence for robust associations with the other seven cancers investigated. Genetically raised bilirubin levels were inversely associated with risk of squamous cell lung cancer as well as Hodgkin's lymphoma and positively associated with risk of breast cancer. Further studies are required to investigate the utility of bilirubin as a low-cost clinical marker to improve risk prediction for certain cancers.

Chromosomal damage measured by the cytokinesis block micronucleus cytome assay in diabetes and obesity - A systematic review and meta-analysis.

The percentage of people affected by overweight, obesity and/or diabetes drastically increased within the last decades. This development is still ongoing, which puts a large part of our society at increased risk for diseases, such as cancer, cardiovascular diseases and cognitive impairment. Especially the development of type 2 diabetes and overweight/obesity could theoretically be prevented. The loss of DNA and genome stability is associated with the above-mentioned metabolic diseases. Insulin resistance, high blood glucose levels or increased body fat are linked to a chronically elevated inflammatory state. This amplifies oxidative stress, might lead to oxidative DNA damage, impairs the cellular proliferation process and results in mutations; all of which increase the possibility for the development of dysfunctional cells, tissue and organs. An established method to measure chromosomal damage is the cytokinesis block micronucleus (CBMN) cytome assay. The aim of this systematic review and meta-analysis is to collect and analyse the current literature of diabetic, obese and overweight patients and their link to cellular mutations measured by the CBMN assay. A clear trend towards increased genome damage in these metabolic diseases was observed. Significantly increased frequencies of chromosomal aberrations were seen in type 2 diabetic subjects (micronuclei frequency: SMD: 1.18, 95% CI: 0.76, 1.60; I2 = 84%). In both, type 1 and type 2 diabetics, disease progression as well as medical quality and quantity were linked to further elevated genome instability. In type 1 diabetic and overweight/obese subjects the number of studies is small and for valid and reliable results more data are needed. Besides the traditionally used material for this method, PBMCs, we extended our analysis to buccal cells in order to qualitatively compare the two cell types. Finally, we discuss knowledge as well as technical/methodical gaps of the CBMN cytome assay and its usability for clinical practice in these metabolic diseases.