Publications by authors named "Heiner Boeing"

868 Publications

Associations between dietary amino acid intakes and blood concentration levels.

Clin Nutr 2021 Jun 27;40(6):3772-3779. Epub 2021 Apr 27.

International Agency for Research on Cancer, Nutrition and Metabolism Section, 69372, Lyon CEDEX 08, France.

Background And Aims: Emerging evidence suggests a role of amino acids (AAs) in the development of various diseases including renal failure, liver cirrhosis, diabetes and cancer. However, mechanistic pathways and the effects of dietary AA intakes on circulating levels and disease outcomes are unclear. We aimed to compare protein and AA intakes, with their respective blood concentrations in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Methods: Dietary protein and AA intakes were assessed via the EPIC dietary questionnaires (DQ) and 24-h dietary recalls (24-HDR). A subsample of 3768 EPIC participants who were free of cancer had blood AA concentrations measured. To investigate how circulating levels relate to their respective intakes, dietary AA intake was examined in quintiles and ANOVA tests were run. Pearson correlations were examined for continous associations between intakes and blood concentrations.

Results: Dietary AA intakes (assessed with the DQ) and blood AA concentrations were not strongly correlated (-0.15 ≤ r ≤ 0.17) and the direction of the correlations depended on AA class: weak positive correlations were found for most essential AAs (isoleucine, leucine, lysine, methionine, threonine, tryptophan, and valine) and conditionally essential AAs (arginine and tyrosine), while negative associations were found for non-essential AAs. Similar results were found when using the 24-HDR. When conducting ANOVA tests for essential AAs, higher intake quintiles were linked to higher blood AA concentrations, except for histidine and phenylalanine. For non-essential AAs and glycine, an inverse relationship was observed. Conditionally-essential AAs showed mixed results.

Conclusions: Weak positive correlations and dose responses were found between most essential and conditionally essential AA intakes, and blood concentrations, but not for the non-essential AAs. These results suggest that intake of dietary AA might be related to physiological AA status, particularly for the essential AAs. However, these results should be further evaluated and confirmed in large-scale prospective studies.
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http://dx.doi.org/10.1016/j.clnu.2021.04.036DOI Listing
June 2021

Dietary Habits and Nutrient Intakes Are Associated to Age-Related Central Auditory Processing Disorder in a Cohort From Southern Italy.

Front Aging Neurosci 2021 6;13:629017. Epub 2021 May 6.

Unit of Research Methodology and Data Sciences for Population Health, "Salus in Apulia Study" National Institute of Gastroenterology "S. de Bellis" Research Hospital, Bari, Italy.

Objectives: Central auditory processing disorder (CAPD) commonly occurs in older age. However, few studies of a possible link between age-related CAPD and diet in an older population have been conducted. The objective of the present study was to investigate the relationship between eating habits and age-related CAPD in a population >65 years, using cross-sectional and retrospective data obtained in the same population-based study about 12 years ago.

Methods: We selected 734 participants (403 men) from a large population-based study. For age-related CAPD assessment, we used the Synthetic Sentence Identification with Ipsilateral Competitive Message test. Dietary habits were assessed by a Food Frequency Questionnaire. Associations between age-related CAPD and food groups/macro-and micronutrients were explored using adjusted logistic regression models.

Results: Age-related CAPD subjects consumed more dairy (111 vs. 98 g/d), olives and vegetable oil (63 vs. 52 g/d) and spirits (2 vs.1 g/d), and less fruits (536 vs. 651 g/d) in the cross-sectional analysis. Age-related CAPD subjects had a lower intake of potassium, vitamin C, and a higher fat intake. Further analyses identified dietary fiber as being inversely related to age-related CAPD.

Discussion: The present study provided evidence that the dietary hypotheses proposed for explaining the development of cognitive disorders in older age might also hold for age-related CAPD. Further data from other large and prospective population-based studies are needed for confirming these findings.
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http://dx.doi.org/10.3389/fnagi.2021.629017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134698PMC
May 2021

A Prospective Diet-Wide Association Study for Risk of Colorectal Cancer in EPIC.

Clin Gastroenterol Hepatol 2021 Apr 24. Epub 2021 Apr 24.

Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Background & Aims: Evidence regarding the association of dietary exposures with colorectal cancer (CRC) risk is not consistent with a few exceptions. Therefore, we conducted a diet-wide association study (DWAS) in the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate the associations between several dietary exposures with CRC risk.

Methods: The association of 92 food and nutrient intakes with CRC risk was assessed in 386,792 participants, 5069 of whom developed incident CRC. Correction for multiple comparisons was performed using the false discovery rate, and emerging associations were examined in the Netherlands Cohort Study (NLCS). Multiplicative gene-nutrient interactions were also tested in EPIC based on known CRC-associated loci.

Results: In EPIC, alcohol, liquor/spirits, wine, beer/cider, soft drinks, and pork were positively associated with CRC, whereas milk, cheese, calcium, phosphorus, magnesium, potassium, riboflavin, vitamin B6, beta carotene, fruit, fiber, nonwhite bread, banana, and total protein intakes were inversely associated. Of these 20 associations, 13 were replicated in the NLCS, for which a meta-analysis was performed, namely alcohol (summary hazard ratio [HR] per 1-SD increment in intake: 1.07; 95% confidence interval [CI], 1.04-1.09), liquor/spirits (HR per 1-SD increment in intake, 1.04; 95% CI, 1.02-1.06), wine (HR per 1-SD increment in intake, 1.04; 95% CI, 1.02-1.07), beer/cider (HR per 1-SD increment in intake, 1.06; 95% CI, 1.04-1.08), milk (HR per 1-SD increment in intake, 0.95; 95% CI, 0.93-0.98), cheese (HR per 1-SD increment in intake, 0.96; 95% CI, 0.94-0.99), calcium (HR per 1-SD increment in intake, 0.93; 95% CI, 0.90-0.95), phosphorus (HR per 1-SD increment in intake, 0.92; 95% CI, 0.90-0.95), magnesium (HR per 1-SD increment in intake, 0.95; 95% CI, 0.92-0.98), potassium (HR per 1-SD increment in intake, 0.96; 95% CI, 0.94-0.99), riboflavin (HR per 1-SD increment in intake, 0.94; 95% CI, 0.92-0.97), beta carotene (HR per 1-SD increment in intake, 0.96; 95% CI, 0.93-0.98), and total protein (HR per 1-SD increment in intake, 0.94; 95% CI, 0.92-0.97). None of the gene-nutrient interactions were significant after adjustment for multiple comparisons.

Conclusions: Our findings confirm a positive association for alcohol and an inverse association for dairy products and calcium with CRC risk, and also suggest a lower risk at higher dietary intakes of phosphorus, magnesium, potassium, riboflavin, beta carotene, and total protein.
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http://dx.doi.org/10.1016/j.cgh.2021.04.028DOI Listing
April 2021

Dietary Macronutrient Composition in Relation to Circulating HDL and Non-HDL Cholesterol: A Federated Individual-Level Analysis of Cross-Sectional Data from Adolescents and Adults in 8 European Studies.

J Nutr 2021 Apr 13. Epub 2021 Apr 13.

Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.

Background: Associations between increased dietary fat and decreased carbohydrate intake with circulating HDL and non-HDL cholesterol have not been conclusively determined.

Objective: We assessed these relations in 8 European observational human studies participating in the European Nutritional Phenotype Assessment and Data Sharing Initiative (ENPADASI) using harmonized data.

Methods: Dietary macronutrient intake was recorded using study-specific dietary assessment tools. Main outcome measures were lipoprotein cholesterol concentrations: HDL cholesterol (mg/dL) and non-HDL cholesterol (mg/dL). A cross-sectional analysis on 5919 participants (54% female) aged 13-80 y was undertaken using the statistical platform DataSHIELD that allows remote/federated nondisclosive analysis of individual-level data. Generalized linear models (GLM) were fitted to assess associations between replacing 5% of energy from carbohydrates with equivalent energy from total fats, SFAs, MUFAs, or PUFAs with circulating HDL cholesterol and non-HDL cholesterol. GLM were adjusted for study source, age, sex, smoking status, alcohol intake and BMI.

Results: The replacement of 5% of energy from carbohydrates with total fats or MUFAs was statistically significantly associated with 0.67 mg/dL (95% CI: 0.40, 0.94) or 0.99 mg/dL (95% CI: 0.37, 1.60) higher HDL cholesterol, respectively, but not with non-HDL cholesterol concentrations. The replacement of 5% of energy from carbohydrates with SFAs or PUFAs was not associated with HDL cholesterol, but SFAs were statistically significantly associated with 1.94 mg/dL (95% CI: 0.08, 3.79) higher non-HDL cholesterol, and PUFAs with -3.91 mg/dL (95% CI: -6.98, -0.84) lower non-HDL cholesterol concentrations. A statistically significant interaction by sex for the association of replacing carbohydrates with MUFAs and non-HDL cholesterol was observed, showing a statistically significant inverse association in males and no statistically significant association in females. We observed no statistically significant interaction by age.

Conclusions: The replacement of dietary carbohydrates with fats had favorable effects on lipoprotein cholesterol concentrations in European adolescents and adults when fats were consumed as MUFAs or PUFAs but not as SFAs.
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http://dx.doi.org/10.1093/jn/nxab077DOI Listing
April 2021

Genetic architectures of proximal and distal colorectal cancer are partly distinct.

Gut 2021 Jul 25;70(7):1325-1334. Epub 2021 Feb 25.

Cancer Prevention and Control Program, Catalan Institute of Oncology - IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.

Objective: An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined.

Design: To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling.

Results: We identified 13 loci that reached genome-wide significance (p<5×10) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer.

Conclusion: Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.
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http://dx.doi.org/10.1136/gutjnl-2020-321534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223655PMC
July 2021

Lifetime alcohol intake, drinking patterns over time and risk of stomach cancer: A pooled analysis of data from two prospective cohort studies.

Int J Cancer 2021 Jun 22;148(11):2759-2773. Epub 2021 Feb 22.

Hellenic Health Foundation, Athens, Greece.

Alcohol consumption is causally linked to several cancers but the evidence for stomach cancer is inconclusive. In our study, the association between long-term alcohol intake and risk of stomach cancer and its subtypes was evaluated. We performed a pooled analysis of data collected at baseline from 491 714 participants in the European Prospective Investigation into Cancer and Nutrition and the Melbourne Collaborative Cohort Study. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for incident stomach cancer in relation to lifetime alcohol intake and group-based life course intake trajectories, adjusted for potential confounders including Helicobacter pylori infection. In all, 1225 incident stomach cancers (78% noncardia) were diagnosed over 7 094 637 person-years; 984 in 382 957 study participants with lifetime alcohol intake data (5 455 507 person-years). Although lifetime alcohol intake was not associated with overall stomach cancer risk, we observed a weak positive association with noncardia cancer (HR = 1.03, 95% CI: 1.00-1.06 per 10 g/d increment), with a HR of 1.50 (95% CI: 1.08-2.09) for ≥60 g/d compared to 0.1 to 4.9 g/d. A weak inverse association with cardia cancer (HR = 0.93, 95% CI: 0.87-1.00) was also observed. HRs of 1.48 (95% CI: 1.10-1.99) for noncardia and 0.51 (95% CI: 0.26-1.03) for cardia cancer were observed for a life course trajectory characterized by heavy decreasing intake compared to light stable intake (P = .02). These associations did not differ appreciably by smoking or H pylori infection status. Limiting alcohol use during lifetime, particularly avoiding heavy use during early adulthood, might help prevent noncardia stomach cancer. Heterogeneous associations observed for cardia and noncardia cancers may indicate etiologic differences.
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http://dx.doi.org/10.1002/ijc.33504DOI Listing
June 2021

Role of plant-based diet in late-life cognitive decline: results from the Salus in Apulia Study.

Nutr Neurosci 2021 Jan 15:1-10. Epub 2021 Jan 15.

Healthy Aging Phenotypes Research Unit - 'Salus in Apulia Study' - National Institute of Gastroenterology 'Saverio de Bellis', Research Hospital, Bari, Italy.

Objectives: Consistency among population-based studies investigating the relationship between diet and cognition in older inhabitants in the Mediterranean area is poor. The present study investigated whether diet changes over 12 years were associated with cognitive function in older people in Southern-Italy.

Methods: From the 'Salus in Apulia Study', that includes the MICOL and GreatAGE Studies, 584 participants were selected, firstly enrolled in MICOL3 (M3) and later in the GreatAGE Study (MICOL4, M4). Foods and micronutrients intake were recorded in both studies, and global cognitive function in M4, assessed with the Mini Mental State Examination.

Results: Plant-based foods, particularly coffee and vegetables, as well as vitamin A sources, were inversely associated to age-related cognitive impairment. Alcohol consumption showed a detrimental role on cognition, while red meat appeared to be beneficial in the present study, although its role is traditionally considered harmful for cognitive function.

Discussion: Our study confirmed that a traditional Mediterranean dietary pattern based on agricultural products and low alcohol consumption may help to prevent/delay age-related cognitive impairment.
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http://dx.doi.org/10.1080/1028415X.2020.1853416DOI Listing
January 2021

Integration of various dimensions in food-based dietary guidelines via mathematical approaches: report of a DGE/FENS Workshop in Bonn, Germany, 23-24 September 2019.

Br J Nutr 2020 Dec 4:1-8. Epub 2020 Dec 4.

MS-Nutrition, 13385Marseille, France.

In the past, food-based dietary guidelines (FBDGs) were derived nearly exclusively by using systematic reviews on diet-health relationships and translating dietary reference values for nutrient intake into foods. This approach neglects many other implications that dietary recommendations have on society, the economy and environment. In view of pressing challenges, such as climate change and the rising burden of diet-related diseases, the simultaneous integration of evidence-based findings from different dimensions into FBDGs is required. Consequently, mathematical methods and data processing are evolving as powerful tools in nutritional sciences. The possibilities and reasons for the derivation of FBDGs via mathematical approaches were the subject of a joint workshop hosted by the German Nutrition Society (DGE) and the Federation of European Nutrition Societies (FENS) in September 2019 in Bonn, Germany. European scientists were invited to discuss and exchange on the topics of mathematical optimisation for the development of FBDGs and different approaches to integrate various dimensions into FBDGs. We concluded that mathematical optimisation is a suitable tool to formulate FBDGs finding trade-offs between conflicting goals and taking several dimensions into account. We identified a lack of evidence for the extent to which constraints and weights for different dimensions are set and the challenge to compile diverse data that suit the demands of optimisation models. We also found that individualisation via mathematical optimisation is one perspective of FBDGs to increase consumer acceptance, but the application of mathematical optimisation for population-based and individual FBDGs requires more experience and evaluation for further improvements.
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http://dx.doi.org/10.1017/S0007114520004857DOI Listing
December 2020

A Cross-Sectional Survey of Salty Snack Consumption among Serbian Urban-Living Students and Their Contribution to Salt Intake.

Nutrients 2020 Oct 27;12(11). Epub 2020 Oct 27.

Department of Bromatology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia.

This study investigated the behavior of urban-living students related to the salty snacks consumption, and their contribution to salt daily intake. A cross-sectional survey on 1313 urban-living students (16-25 years, 61.4% university students and 38.6% high school students) used a pre-verified questionnaire created specifically for the study. The logistic regression analysis was performed to investigate the factors influencing snack consumption. The results of salt content and the snack consumption frequency were used to evaluate snack contribution to salt intake. All subjects consumed salty snacks, on average several times per week, more often at home and slightly more during periods of intensive studying, with 42% of the participants reporting to consume two or more packages per snacking occasion. Most of the participants consumed such products between main meals, but 10% of them took snacks immediately after the main meal. More high-school students than university students were in the "high snack group" ( < 0.05). The most frequently consumed salty snacks were those with the highest content of salt. Salt intake from snack products for a majority of participants ranged between 0.4 and 1 g/day. The research revealed younger age, home environment and significant contribution to salt intake as critical points in salty snack consumption among urban-living students important for the better understanding of their dietary habits.
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http://dx.doi.org/10.3390/nu12113290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692209PMC
October 2020

The association between circulating 25-hydroxyvitamin D metabolites and type 2 diabetes in European populations: A meta-analysis and Mendelian randomisation analysis.

PLoS Med 2020 10 16;17(10):e1003394. Epub 2020 Oct 16.

Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.

Background: Prior research suggested a differential association of 25-hydroxyvitamin D (25(OH)D) metabolites with type 2 diabetes (T2D), with total 25(OH)D and 25(OH)D3 inversely associated with T2D, but the epimeric form (C3-epi-25(OH)D3) positively associated with T2D. Whether or not these observational associations are causal remains uncertain. We aimed to examine the potential causality of these associations using Mendelian randomisation (MR) analysis.

Methods And Findings: We performed a meta-analysis of genome-wide association studies for total 25(OH)D (N = 120,618), 25(OH)D3 (N = 40,562), and C3-epi-25(OH)D3 (N = 40,562) in participants of European descent (European Prospective Investigation into Cancer and Nutrition [EPIC]-InterAct study, EPIC-Norfolk study, EPIC-CVD study, Ely study, and the SUNLIGHT consortium). We identified genetic variants for MR analysis to investigate the causal association of the 25(OH)D metabolites with T2D (including 80,983 T2D cases and 842,909 non-cases). We also estimated the observational association of 25(OH)D metabolites with T2D by performing random effects meta-analysis of results from previous studies and results from the EPIC-InterAct study. We identified 10 genetic loci associated with total 25(OH)D, 7 loci associated with 25(OH)D3 and 3 loci associated with C3-epi-25(OH)D3. Based on the meta-analysis of observational studies, each 1-standard deviation (SD) higher level of 25(OH)D was associated with a 20% lower risk of T2D (relative risk [RR]: 0.80; 95% CI 0.77, 0.84; p < 0.001), but a genetically predicted 1-SD increase in 25(OH)D was not significantly associated with T2D (odds ratio [OR]: 0.96; 95% CI 0.89, 1.03; p = 0.23); this result was consistent across sensitivity analyses. In EPIC-InterAct, 25(OH)D3 (per 1-SD) was associated with a lower risk of T2D (RR: 0.81; 95% CI 0.77, 0.86; p < 0.001), while C3-epi-25(OH)D3 (above versus below lower limit of quantification) was positively associated with T2D (RR: 1.12; 95% CI 1.03, 1.22; p = 0.006), but neither 25(OH)D3 (OR: 0.97; 95% CI 0.93, 1.01; p = 0.14) nor C3-epi-25(OH)D3 (OR: 0.98; 95% CI 0.93, 1.04; p = 0.53) was causally associated with T2D risk in the MR analysis. Main limitations include the lack of a non-linear MR analysis and of the generalisability of the current findings from European populations to other populations of different ethnicities.

Conclusions: Our study found discordant associations of biochemically measured and genetically predicted differences in blood 25(OH)D with T2D risk. The findings based on MR analysis in a large sample of European ancestry do not support a causal association of total 25(OH)D or 25(OH)D metabolites with T2D and argue against the use of vitamin D supplementation for the prevention of T2D.
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http://dx.doi.org/10.1371/journal.pmed.1003394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567390PMC
October 2020

Traditional Old Dietary Pattern of Castellana Grotte (Apulia) Is Associated with Healthy Outcomes.

Nutrients 2020 Oct 12;12(10). Epub 2020 Oct 12.

Unit of Epidemiology and Biostatistics, National Institute of Gastroenterology "Saverio de Bellis", Research Hospital, Castellana Grotte, 70013 Bari, Italy.

Background: There is still room for further studies aimed at investigating the most widespread diets in the Mediterranean area. The objective of the study is to analyze the relation of food group intake to clinical chemical indicators of health, and also to compare the food group intake with healthy well-known diet indices.

Methods: Lifestyle, dietary, and clinical data collected in 2005/2006 and 2012/2018 from Castellana Grotte, located in the rural area of Apulia, were analyzed. The study populations included newly recruited subjects at each time period (n = 1870) as well as subjects examined twice and compared over time regarding health indicators (n = 734). Diet was assessed through a validated food frequency questionnaire. Three healthy diet indices were calculated and related to 29 food groups. We also performed prospective regression of food group consumption with health indicators.

Results: The diet over the time period of observation was very stable and consisted of a high proportion of vegetables, fruit and grains. No major changes in body mass index (BMI) and blood pressure were observed. Consumption of low-fat dairy, juices, olive oil, and water were related to reductions in weight gain, systolic blood pressure, high-density lipoprotein (HDL)-cholesterol and cholesterol (total and HDL) levels, in that order. Over the time periods we observed only a slight decrease of adherence to the Meddietscore. The correlations of the healthy diet indices with food groups revealed some differences among the indices, mostly regarding the intake of fruit and vegetables.

Conclusions: The dietary pattern of Apulia is in line with many principles of a healthy diet and the cohort population seems to be less liable to undergo a transition to a westernized diet.
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http://dx.doi.org/10.3390/nu12103097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600964PMC
October 2020

Association of familial history of diabetes or myocardial infarction and stroke with risk of cardiovascular diseases in four German cohorts.

Sci Rep 2020 09 21;10(1):15373. Epub 2020 Sep 21.

Department of Food Safety, German Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, Berlin, Germany.

Since family history of diabetes is a very strong risk factor for type 2 diabetes, which is one of the most important risk factors for cardiovascular disease (CVD), it might be also useful to assess the risk for CVD. Therefore, we aimed to investigate the relationship between a familial (parents and siblings) history of diabetes and the risk of incident CVD. Data from four prospective German cohort studies were used: EPIC-Potsdam study (n = 26,054), CARLA study (n = 1,079), SHIP study (n = 3,974), and KORA study (n = 15,777). A multivariable-adjusted Cox regression was performed to estimate associations between familial histories of diabetes, myocardial infarction or stroke and the risk of CVD in each cohort; combined hazard ratios (HR) were derived by conducting a meta-analysis. The history of diabetes in first-degree relatives was not related to the development of CVD (HR 0.99; 95% CI 0.88-1.10). Results were similar for the single outcomes myocardial infarction (MI) (HR 1.07; 95% CI 0.92-1.23) and stroke (HR 1.00; 95% CI 0.86-1.16). In contrast, parental history of MI and stroke were associated with an increased CVD risk. Our study indicates that diabetes in the family might not be a relevant risk factor for the incidence of CVD. However, the study confirmed the relationship between a parental history of MI or stroke and the onset of CVD.
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http://dx.doi.org/10.1038/s41598-020-72361-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505832PMC
September 2020

Circulating bilirubin levels and risk of colorectal cancer: serological and Mendelian randomization analyses.

BMC Med 2020 09 3;18(1):229. Epub 2020 Sep 3.

Public Health Directorate, Asturias, Spain.

Background: Bilirubin, a byproduct of hemoglobin breakdown and purported anti-oxidant, is thought to be cancer preventive. We conducted complementary serological and Mendelian randomization (MR) analyses to investigate whether alterations in circulating levels of bilirubin are associated with risk of colorectal cancer (CRC). We decided a priori to perform analyses separately in men and women based on suggestive evidence that associations may differ by sex.

Methods: In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC), pre-diagnostic unconjugated bilirubin (UCB, the main component of total bilirubin) concentrations were measured by high-performance liquid chromatography in plasma samples of 1386 CRC cases and their individually matched controls. Additionally, 115 single-nucleotide polymorphisms (SNPs) robustly associated (P < 5 × 10) with circulating total bilirubin were instrumented in a 2-sample MR to test for a potential causal effect of bilirubin on CRC risk in 52,775 CRC cases and 45,940 matched controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colon Cancer Family Registry (CCFR), and the Colorectal Transdisciplinary (CORECT) study.

Results: The associations between circulating UCB levels and CRC risk differed by sex (P = 0.008). Among men, higher levels of UCB were positively associated with CRC risk (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.04-1.36; per 1-SD increment of log-UCB). In women, an inverse association was observed (OR = 0.86 (0.76-0.97)). In the MR analysis of the main UGT1A1 SNP (rs6431625), genetically predicted higher levels of total bilirubin were associated with a 7% increase in CRC risk in men (OR = 1.07 (1.02-1.12); P = 0.006; per 1-SD increment of total bilirubin), while there was no association in women (OR = 1.01 (0.96-1.06); P = 0.73). Raised bilirubin levels, predicted by instrumental variables excluding rs6431625, were suggestive of an inverse association with CRC in men, but not in women. These differences by sex did not reach formal statistical significance (P ≥ 0.2).

Conclusions: Additional insight into the relationship between circulating bilirubin and CRC is needed in order to conclude on a potential causal role of bilirubin in CRC development.
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http://dx.doi.org/10.1186/s12916-020-01703-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469292PMC
September 2020

Nutritional domains in frailty tools: Working towards an operational definition of nutritional frailty.

Ageing Res Rev 2020 12 19;64:101148. Epub 2020 Aug 19.

Healthy Aging Phenotypes Research Unit, "Salus in Apulia Study", National Institute of Gastroenterology "Saverio de Bellis", Research Hospital, Castellana Grotte, Bari, Italy; Neurodegenerative Disease Unit, Department of Basic Medicine, Neuroscience, and Sense Organs, University of Bari Aldo Moro, Bari, Italy. Electronic address:

Different methods have been proposed for the assessment of the nutritional status in frailty phenotypes. In the present narrative review article, we have summarized the number and specifications of nutritional items in existing frailty tools, in order to develop a possible means of assessment and operational definition of the nutritional frailty phenotype. In six different databases until December 2019, we searched for original articles regarding frailty tools (i.e., scales, indexes, scores, questionnaires, instruments, evaluations, screening, indicators), analyzing each tool regarding nutritional items. We identified 160 articles describing 71 frailty tools. Among the selected frailty tools, 54 were community-based (70 %), 17 hospital-based (22 %), 4 validated in long-term care institutions for older adults (LTCIOA) (5.1 %) and 2 validated in both community- and hospital-based settings, including LTCIOA (2.5 %). Fifty-two of these tools (73 %) included at least one nutritional item. Twenty-two (42 %) reported two or more nutritional items. The items were grouped in the following categories: A) anthropometric measurements, B) laboratory measurements, and C) other nutritional-related measurements. Anthropometric measurements stood out compared to all other items. Nutritional items are included in the majority of frailty tools, strengthening the concept that they may have a direct implication on an increased risk of adverse health-related outcomes in frail subjects. This supports the development of the concept of nutritional frailty as an independent frailty phenotype. Subsequent steps will be to assess the contribution of each nutritional item to a possible operational definition of nutritional frailty and define the items that may best identify this new frailty phenotype.
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http://dx.doi.org/10.1016/j.arr.2020.101148DOI Listing
December 2020

Opposing Associations of NT-proBNP With Risks of Diabetes and Diabetes-Related Complications.

Diabetes Care 2020 12 17;43(12):2930-2937. Epub 2020 Aug 17.

Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany

Objective: Circulating N-terminal pro B-type natriuretic peptide (NT-proBNP) is a classic diagnostic and prognostic marker for heart failure. However, it is inversely associated with diabetes risk. We aimed to investigate relationships of NT-proBNP with risk of diabetes-related complications in initially healthy individuals.

Research Design And Methods: We performed a case-cohort study within the European Prospective Investigation Into Cancer and Nutrition (EPIC)-Potsdam cohort including a random subcohort ( = 1,294) and incident cases of type 2 diabetes ( = 649) and cardiovascular diseases ( = 478). Incident cases of type 2 diabetes ( = 545) were followed up for microvascular ( = 133) and macrovascular ( = 50) complications. Plasma NT-proBNP was measured at baseline in initially healthy participants.

Results: In multivariable models, NT-proBNP was linearly inversely associated with incident type 2 diabetes with a hazard ratio (HR) (95% CI) per doubling in NT-proBNP of 0.91 (0.86, 0.98). The association was only observable in women (0.80 [0.72, 0.90]) compared with men (0.98 [0.91, 1.07]). Among people with incident diabetes, NT-proBNP was positively associated with diabetes complications: overall, 1.31 (1.13, 1.53); microvascular complications, 1.20 (1.01, 1.43); and macrovascular complications, 1.37 (1.03, 1.83).

Conclusions: Although higher NT-proBNP levels are associated with lower diabetes risk, NT-proBNP is a biomarker for vascular complications in people who develop diabetes independent of potential confounders. Thus, NT-proBNP might be informative to monitor risk for diabetes-related microvascular and macrovascular complications, which should be further explored in future prospective studies.
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http://dx.doi.org/10.2337/dc20-0553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770272PMC
December 2020

Mediating effect of soluble B-cell activation immune markers on the association between anthropometric and lifestyle factors and lymphoma development.

Sci Rep 2020 08 14;10(1):13814. Epub 2020 Aug 14.

Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, P.O. Box 80178, 3508 TD, Utrecht, The Netherlands.

Sustained B-cell activation is an important mechanism contributing to B-cell lymphoma (BCL). We aimed to validate four previously reported B-cell activation markers predictive of BCL risk (sCD23, sCD27, sCD30, and CXCL13) and to examine their possible mediating effects on the association between anthropometric and lifestyle factors and major BCL subtypes. Pre-diagnostic serum levels were measured for 517 BCL cases and 525 controls in a nested case-control study. The odds ratios of BCL were 6.2 in the highest versus lowest quartile for sCD23, 2.6 for sCD30, 4.2 for sCD27, and 2.6 for CXCL13. Higher levels of all markers were associated with increased risk of chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). Following mutual adjustment for the other immune markers, sCD23 remained associated with all subtypes and CXCL13 with FL and DLBCL. The associations of sCD23 with CLL and DLBCL and CXCL13 with DLBCL persisted among cases sampled > 9 years before diagnosis. sCD23 showed a good predictive ability (area under the curve = 0.80) for CLL, in particular among older, male participants. sCD23 and CXCL13 showed a mediating effect between body mass index (positive) and DLBCL risk, while CXCL13 contributed to the association between physical activity (inverse) and DLBCL. Our data suggest a role of B-cell activation in BCL development and a mediating role of the immune system for lifestyle factors.
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http://dx.doi.org/10.1038/s41598-020-70790-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429856PMC
August 2020

Association of plasma biomarkers of fruit and vegetable intake with incident type 2 diabetes: EPIC-InterAct case-cohort study in eight European countries.

BMJ 2020 07 8;370:m2194. Epub 2020 Jul 8.

Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Objective: To investigate the association of plasma vitamin C and carotenoids, as indicators of fruit and vegetable intake, with the risk of type 2 diabetes.

Design: Prospective case-cohort study.

Setting: Populations from eight European countries.

Participants: 9754 participants with incident type 2 diabetes, and a subcohort of 13 662 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort of 340 234 participants: EPIC-InterAct case-cohort study.

Main Outcome Measure: Incident type 2 diabetes.

Results: In a multivariable adjusted model, higher plasma vitamin C was associated with a lower risk of developing type 2 diabetes (hazard ratio per standard deviation 0.82, 95% confidence interval 0.76 to 0.89). A similar inverse association was shown for total carotenoids (hazard ratio per standard deviation 0.75, 0.68 to 0.82). A composite biomarker score (split into five equal groups), comprising vitamin C and individual carotenoids, was inversely associated with type 2 diabetes with hazard ratios 0.77, 0.66, 0.59, and 0.50 for groups 2-5 compared with group 1 (the lowest group). Self-reported median fruit and vegetable intake was 274 g/day, 396 g/day, and 508 g/day for participants in categories defined by groups 1, 3, and 5 of the composite biomarker score, respectively. One standard deviation difference in the composite biomarker score, equivalent to a 66 (95% confidence interval 61 to 71) g/day difference in total fruit and vegetable intake, was associated with a hazard ratio of 0.75 (0.67 to 0.83). This would be equivalent to an absolute risk reduction of 0.95 per 1000 person years of follow up if achieved across an entire population with the characteristics of the eight European countries included in this analysis.

Conclusions: These findings indicate an inverse association between plasma vitamin C, carotenoids, and their composite biomarker score, and incident type 2 diabetes in different European countries. These biomarkers are objective indicators of fruit and vegetable consumption, and suggest that diets rich in even modestly higher fruit and vegetable consumption could help to prevent development of type 2 diabetes.
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http://dx.doi.org/10.1136/bmj.m2194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341350PMC
July 2020

Food-Based Dietary Guidelines - development of a conceptual framework for future Food-Based Dietary Guidelines in Europe: report of a Federation of European Nutrition Societies Task-Force Workshop in Copenhagen, 12-13 March 2018.

Br J Nutr 2020 12 6;124(12):1338-1344. Epub 2020 Jul 6.

German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany.

Identifying a need for developing a conceptual framework for the future development of Food-Based Dietary Guidelines (FBDG) in Europe, The Federation of European Nutrition Sciences established a Task Force for this purpose. A workshop was held with the specific objective to discuss the various dimensions considered as particularly relevant. Existing frameworks for FBDG were discussed, and presentations from various countries illustrated not only several commonalities but also a high degree of heterogeneity in the guidelines from different countries. Environmental aspects were considered in several countries, and dimensions like food safety, dietary habits and preparation were included in others. The workshop provided an overview of the use of FBDG - both in developing front-of-pack nutrition labels and for reformulation and innovation. The European FBDG dimensions were described with examples from the close connection between FBDG and European Union (EU) policies and activities and from the compilation of a database of national FBDG. Also, the challenges with communication of FBDG were discussed. Considering the current scientific basis and the experiences from several countries, the Task Force discussed the various dimensions of developing FBDG and concluded that environmental aspects should be included in the future conceptual framework for FBDG. A change in terminology to sustainable FDBG (SFBDG) could reflect this. The Task Force concluded that further work needs to be done exploring current practice, existing methodologies and the future prospects for incorporating other relevant dimensions into a future Federation of European Nutrition Societies conceptual framework for SFBDG in Europe and working groups were formed to address that.
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http://dx.doi.org/10.1017/S0007114520002469DOI Listing
December 2020

Dietary and Circulating Fatty Acids and Ovarian Cancer Risk in the European Prospective Investigation into Cancer and Nutrition.

Cancer Epidemiol Biomarkers Prev 2020 09 2;29(9):1739-1749. Epub 2020 Jul 2.

Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology - ICO, Group of Research on Nutrition and Cancer, Bellvitge Biomedical Research Institute - IDIBELL, L'Hospitalet of Llobregat, Barcelona, Spain.

Background: Fatty acids impact obesity, estrogens, and inflammation, which are risk factors for ovarian cancer. Few epidemiologic studies have investigated the association of fatty acids with ovarian cancer.

Methods: Within the European Prospective Investigation into Cancer and Nutrition (EPIC), 1,486 incident ovarian cancer cases were identified. Cox proportional hazard models with adjustment for ovarian cancer risk factors were used to estimate HRs of ovarian cancer across quintiles of intake of fatty acids. False discovery rate was computed to control for multiple testing. Multivariable conditional logistic regression models were used to estimate ORs of ovarian cancer across tertiles of plasma fatty acids among 633 cases and two matched controls in a nested case-control analysis.

Results: A positive association was found between ovarian cancer and intake of industrial elaidic acid [HR comparing fifth with first quintile = 1.29; 95% confidence interval (CI) = 1.03-1.62; = 0.02, q-value = 0.06]. Dietary intakes of -6 linoleic acid (HR = 1.10; 95% CI = 1.01-1.21; = 0.03) and -3 α-linolenic acid (HR = 1.18; 95% CI = 1.05-1.34; = 0.007) from deep-frying fats were also positively associated with ovarian cancer. Suggestive associations were reported for circulating elaidic (OR comparing third with first tertile = 1.39; 95% CI = 0.99-1.94; = 0.06) and α-linolenic acids (OR = 1.30; 95% CI = 0.98-1.72; = 0.06).

Conclusions: Our results suggest that higher intakes and circulating levels of industrial elaidic acid, and higher intakes of linoleic acid and α-linolenic acid from deep-frying fat, may be associated with greater risk of ovarian cancer.

Impact: If causal, eliminating industrial -fatty acids could offer a straightforward public health action for reducing ovarian cancer risk.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-1477DOI Listing
September 2020

Menstrual Factors, Reproductive History, Hormone Use, and Urothelial Carcinoma Risk: A Prospective Study in the EPIC Cohort.

Cancer Epidemiol Biomarkers Prev 2020 08 28;29(8):1654-1664. Epub 2020 May 28.

Hellenic Health Foundation, Kaisareias 13 & Alexandroupoleos, Athens, Greece.

Background: Urothelial carcinoma is the predominant (95%) bladder cancer subtype in industrialized nations. Animal and epidemiologic human studies suggest that hormonal factors may influence urothelial carcinoma risk.

Methods: We used an analytic cohort of 333,919 women from the European Prospective Investigation into Cancer and Nutrition Cohort. Associations between hormonal factors and incident urothelial carcinoma (overall and by tumor grade, tumor aggressiveness, and non-muscle-invasive urothelial carcinoma) risk were evaluated using Cox proportional hazards models.

Results: During a mean of 15 years of follow-up, 529 women developed urothelial carcinoma. In a model including number of full-term pregnancies (FTP), menopausal status, and menopausal hormone therapy (MHT), number of FTP was inversely associated with urothelial carcinoma risk (HR = 0.48; 0.25-0.90; in parous women = 0.010) and MHT use (compared with nonuse) was positively associated with urothelial carcinoma risk (HR = 1.27; 1.03-1.57), but no dose response by years of MHT use was observed. No modification of HRs by smoking status was observed. Finally, sensitivity analyses in never smokers showed similar HR patterns for the number of FTP, while no association between MHT use and urothelial carcinoma risk was observed. Association between MHT use and urothelial carcinoma risk remained significant only in current smokers. No heterogeneity of the risk estimations in the final model was observed by tumor aggressiveness or by tumor grade. A positive association between MTH use and non-muscle-invasive urothelial carcinoma risk was observed.

Conclusions: Our results support that increasing the number of FTP may reduce urothelial carcinoma risk.

Impact: More detailed studies on parity are needed to understand the possible effects of perinatal hormone changes in urothelial cells.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0184DOI Listing
August 2020

Antibody Responses to and Risk of Developing Colorectal Cancer in a European Cohort.

Cancer Epidemiol Biomarkers Prev 2020 07 24;29(7):1475-1481. Epub 2020 Apr 24.

CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain.

Background: While () is the major cause of gastric cancer, it has also been suggested to be involved in colorectal cancer development. However, prospective studies addressing and colorectal cancer are sparse and inconclusive. We assessed the association of antibody responses to proteins with colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Methods: We applied multiplex serology to measure antibody responses to 13 proteins in prediagnostic serum samples from 485 colorectal cancer cases and 485 matched controls nested within the EPIC study. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable conditional logistic regression to estimate the association of overall and protein-specific seropositivity with odds of developing colorectal cancer.

Results: Fifty-one percent of colorectal cancer cases were seropositive compared with 44% of controls, resulting in an OR of 1.36 (95% CI, 1.00-1.85). Among the 13 individual proteins, the association was driven mostly by seropositivity to cysteine-rich protein C (HcpC; OR: 1.66; 95% CI, 1.19-2.30) and Vacuolating cytotoxin A (VacA) (OR: 1.34; 95% CI, 0.99-1.82), the latter being nonstatistically significant only in the fully adjusted model.

Conclusions: In this prospective multicenter European study, antibody responses to proteins, specifically HcpC and VacA, were associated with an increased risk of developing colorectal cancer.

Impact: Biological mechanisms for a potential causal role of in colorectal carcinogenesis need to be elucidated, and subsequently whether eradication may decrease colorectal cancer incidence.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-1545DOI Listing
July 2020

Traditional Dietary Patterns and Risk of Mortality in a Longitudinal Cohort of the Salus in Apulia Study.

Nutrients 2020 Apr 12;12(4). Epub 2020 Apr 12.

Scientific direction, National Institute of Gastroenterology "Saverio de Bellis", Research Hospital, Castellana Grotte, 70013 Bari, Italy.

There is still room for further studies analyzing the long-term health impact of specific dietary patterns observable in regions belonging to the Mediterranean area. The aim of the study is to evaluate how much a diet practiced in southern Italy is associated to a risk of mortality. The study population included 2472 participants first investigated in 1985, inquiring about their frequencies of intake of 29 foods using a self-administered questionnaire covering the previous year. The population was followed up for mortality until 31 December 2017. Cox-based risk modeling referred to single foods, food groups, the results of principal component analysis (PCA), and a priori indexes. Single food analysis revealed eggs, fatty meat, and fatty/baked ham to be inversely associated with mortality. Furthermore, one of the 5 PCA derived dietary patterns, the "Farmhouse" pattern, showed a higher hazard ratio (HR), mostly driven by dairy products. In subsequent analyses, the increased risk of mortality for fresh cheese and decreased risk for fatty ham and eggs were confirmed. The a priori diet indexes (Italian Meddiet, Meddietscore, Dietary Approaches to Stop Hypertension (DASH), and Mediterranean-DASH Intervention for Neurodegenerative Delay diet (MIND) indexes) showed borderline inverse relationships. In a Mediterranean population with an overall healthy diet, foods such as eggs and fatty meat, reflecting dietary energy and wealth, played a role in prolonging the life of individuals. Our study confirms that some dairy products might have a detrimental role in mortality in the Mediterranean setting.
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http://dx.doi.org/10.3390/nu12041070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230634PMC
April 2020

Serologic markers of Chlamydia trachomatis and other sexually transmitted infections and subsequent ovarian cancer risk: Results from the EPIC cohort.

Int J Cancer 2020 10 24;147(8):2042-2052. Epub 2020 Apr 24.

Clinical Microbiology, Department of Translational Medicine, Lund University, Malmö, Sweden.

A substantial proportion of epithelial ovarian cancer (EOC) arises in the fallopian tube and other epithelia of the upper genital tract; these epithelia may incur damage and neoplastic transformation after sexually transmitted infections (STI) and pelvic inflammatory disease. We investigated the hypothesis that past STI infection, particularly Chlamydia trachomatis, is associated with higher EOC risk in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort including 791 cases and 1669 matched controls. Serum antibodies against C. trachomatis, Mycoplasma genitalium, herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) 16, 18 and 45 were assessed using multiplex fluorescent bead-based serology. Conditional logistic regression was used to estimate relative risks (RR) and 95% confidence intervals (CI) comparing women with positive vs. negative serology. A total of 40% of the study population was seropositive to at least one STI. Positive serology to C. trachomatis Pgp3 antibodies was not associated with EOC risk overall, but with higher risk of the mucinous histotype (RR = 2.30 [95% CI = 1.22-4.32]). Positive serology for chlamydia heat shock protein 60 (cHSP60-1) was associated with higher risk of EOC overall (1.36 [1.13-1.64]) and with the serous subtype (1.44 [1.12-1.85]). None of the other evaluated STIs were associated with EOC risk overall; however, HSV-2 was associated with higher risk of endometrioid EOC (2.35 [1.24-4.43]). The findings of our study suggest a potential role of C. trachomatis in the carcinogenesis of serous and mucinous EOC, while HSV-2 might promote the development of endometrioid disease.
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http://dx.doi.org/10.1002/ijc.32999DOI Listing
October 2020

Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length.

Am J Hum Genet 2020 03 27;106(3):389-404. Epub 2020 Feb 27.

Department of Cardiovascular Sciences, University of Leicester, LE3 9QP, United Kingdom; NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, LE3 9QP, United Kingdom.

Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1, PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.
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http://dx.doi.org/10.1016/j.ajhg.2020.02.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058826PMC
March 2020

The associations of major foods and fibre with risks of ischaemic and haemorrhagic stroke: a prospective study of 418 329 participants in the EPIC cohort across nine European countries.

Eur Heart J 2020 07;41(28):2632-2640

Department of Public Health and Clinical Medicine, Umeå University, 901 87 Umeå, Sweden.

Aim: To investigate the associations between major foods and dietary fibre with subtypes of stroke in a large prospective cohort.

Methods And Results: We analysed data on 418 329 men and women from nine European countries, with an average of 12.7 years of follow-up. Diet was assessed using validated country-specific questionnaires which asked about habitual intake over the past year, calibrated using 24-h recalls. Multivariable-adjusted Cox regressions were used to estimate hazard ratios (HRs) for ischaemic and haemorrhagic stroke associated with consumption of red and processed meat, poultry, fish, dairy foods, eggs, cereals, fruit and vegetables, legumes, nuts and seeds, and dietary fibre. For ischaemic stroke (4281 cases), lower risks were observed with higher consumption of fruit and vegetables combined (HR; 95% CI per 200 g/day higher intake, 0.87; 0.82-0.93, P-trend < 0.001), dietary fibre (per 10 g/day, 0.77; 0.69-0.86, P-trend < 0.001), milk (per 200 g/day, 0.95; 0.91-0.99, P-trend = 0.02), yogurt (per 100 g/day, 0.91; 0.85-0.97, P-trend = 0.004), and cheese (per 30 g/day, 0.88; 0.81-0.97, P-trend = 0.008), while higher risk was observed with higher red meat consumption which attenuated when adjusted for the other statistically significant foods (per 50 g/day, 1.07; 0.96-1.20, P-trend = 0.20). For haemorrhagic stroke (1430 cases), higher risk was associated with higher egg consumption (per 20 g/day, 1.25; 1.09-1.43, P-trend = 0.002).

Conclusion: Risk of ischaemic stroke was inversely associated with consumption of fruit and vegetables, dietary fibre, and dairy foods, while risk of haemorrhagic stroke was positively associated with egg consumption. The apparent differences in the associations highlight the importance of examining ischaemic and haemorrhagic stroke subtypes separately.
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http://dx.doi.org/10.1093/eurheartj/ehaa007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377582PMC
July 2020

Relationship between Inflammatory Food Consumption and Age-Related Hearing Loss in a Prospective Observational Cohort: Results from the Salus in Apulia Study.

Nutrients 2020 Feb 7;12(2). Epub 2020 Feb 7.

Otolaryngology Unit, Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari Aldo Moro, 70100 Bari, Italy.

Age related hearing loss (ARHL) affects about one third of the elderly population. It is suggested that the senescence of the hair cells could be modulated by inflammation. Thus, intake of anti- and pro-inflammatory foods is of high interest.

Methods: From the MICOL study population, 734 participants were selected that participated in the 2013 to 2018 examination including hearing ability and from which past data collected in 2005/2008 was available. ARHL status was determined and compared cross-sectionally and retrospectively according to clinical and lifestyle data including food and micronutrient intake.

Results: ARHL status was associated with higher age but not with education, smoking, relative weight (BMI), and clinical-chemical blood markers in the crossectional and retrospective analyses. Higher intake of fruit juices among ARHL-participants was seen cross-sectionally, and of sugary foods, high-caloric drinks, beer, and spirits retrospectively. No difference was found for the other 26 food groups and for dietary micronutrients with the exception of past vitamin A, which was higher among normal hearing subjects.

Conclusions: Pro-inflammatory foods with a high-sugar content and also beer and spirits were found to be assocated with positive ARHL-status, but not anti-inflammatory foods. Diet could be a candidate for lifestyle advice for the prevention of ARHL.
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http://dx.doi.org/10.3390/nu12020426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071162PMC
February 2020

Serum levels of hsa-miR-16-5p, hsa-miR-29a-3p, hsa-miR-150-5p, hsa-miR-155-5p and hsa-miR-223-3p and subsequent risk of chronic lymphocytic leukemia in the EPIC study.

Int J Cancer 2020 09 2;147(5):1315-1324. Epub 2020 Mar 2.

Centro de Investigación Biomédica en Red: Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.

Chronic lymphocytic leukemia (CLL) is an incurable disease accounting for almost one-third of leukemias in the Western world. Aberrant expression of microRNAs (miRNAs) is a well-established characteristic of CLL, and the robust nature of miRNAs makes them eminently suitable liquid biopsy biomarkers. Using a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC), the predictive values of five promising human miRNAs (hsa-miR-16-5p, hsa-miR-29a-3p, hsa-miR-150-5p, hsa-miR-155-5p and hsa-miR-223-3p), identified in a pilot study, were examined in serum of 224 CLL cases (diagnosed 3 months to 18 years after enrollment) and 224 matched controls using Taqman based assays. Conditional logistic regressions were applied to adjust for potential confounders. The median time from blood collection to CLL diagnosis was 10 years (p25-p75: 7-13 years). Overall, the upregulation of hsa-miR-150-5p, hsa-miR-155-5p and hsa-miR-29a-3p was associated with subsequent risk of CLL [OR (95%CI) = 1.42 (1.18-1.72), 1.64 (1.31-2.04) and 1.75 (1.31-2.34) for hsa-miR-150-5p, hsa-miR-155-5p and hsa-miR-29a-3p, respectively] and the strongest associations were observed within 10 years of diagnosis. However, the predictive performance of these miRNAs was modest (area under the curve <0.62). hsa-miR-16-5p and hsa-miR-223-3p levels were unrelated to CLL risk. The findings of this first prospective study suggest that hsa-miR-29a, hsa-miR-150-5p and hsa-miR-155-5p were upregulated in early stages of CLL but were modest predictive biomarkers of CLL risk.
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http://dx.doi.org/10.1002/ijc.32894DOI Listing
September 2020

Factors associated with habitual time spent in different physical activity intensities using multiday accelerometry.

Sci Rep 2020 01 21;10(1):774. Epub 2020 Jan 21.

Molecular Epidemiology Group, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.

To investigate factors associated with time in physical activity intensities, we assessed physical activity of 249 men and women (mean age 51.3 years) by 7-day 24h-accelerometry (ActiGraph GT3X+). Triaxial vector magnitude counts/minute were extracted to determine time in inactivity, in low-intensity, moderate, and vigorous-to-very-vigorous activity. Cross-sectional associations with sex, age, body mass index, waist circumference, smoking, alcohol consumption, education, employment, income, marital status, diabetes, and dyslipidaemia were investigated in multivariable regression analyses. Higher age was associated with more time in low-intensity (mean difference, 7.3 min/d per 5 years; 95% confidence interval 2.0,12.7) and less time in vigorous-to-very-vigorous activity (-0.8 min/d; -1.4, -0.2), while higher BMI was related to less time in low-intensity activity (-3.7 min/d; -6.3, -1.2). Current versus never smoking was associated with more time in low-intensity (29.2 min/d; 7.5, 50.9) and less time in vigorous-to-very-vigorous activity (-3.9 min/d; -6.3, -1.5). Finally, having versus not having a university entrance qualification and being not versus full time employed were associated with more inactivity time (35.9 min/d; 13.0, 58.8, and 66.2 min/d; 34.7, 97.7, respectively) and less time in low-intensity activity (-31.7 min/d; -49.9, -13.4, and -50.7; -76.6, -24.8, respectively). The assessed factors show distinct associations with activity intensities, providing targets for public health measures aiming to increase activity.
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http://dx.doi.org/10.1038/s41598-020-57648-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6972881PMC
January 2020

Inflammatory potential of the diet and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition study.

Int J Cancer 2020 08 31;147(4):1027-1039. Epub 2020 Jan 31.

CESP, Faculté de Médecine, Université Paris-Sud, UVSQ, INSERM, Université Paris-Saclay, Villejuif, France.

Proinflammatory diets are associated with risk of developing colorectal cancer (CRC), however, inconsistencies exist in subsite- and sex-specific associations. The relationship between CRC and combined lifestyle-related factors that contribute toward a low-grade inflammatory profile has not yet been explored. We examined the association between the dietary inflammatory potential and an inflammatory profile and CRC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. This cohort included 476,160 participants followed-up of 14 years and 5,991 incident CRC cases (3,897 colon and 2,094 rectal tumors). Dietary inflammatory potential was estimated using an Inflammatory Score of the Diet (ISD). An Inflammatory Profile Score (IPS) was constructed, incorporating the ISD, physical activity level and abdominal obesity. The associations between the ISD and CRC and IPS and CRC were assessed using multivariable regression models. More proinflammatory diets were related to a higher CRC risk, particularly for colon cancer; hazard ratio (HR) for highest versus lowest ISD quartile was 1.15 (95% confidence interval [CI] 1.04-1.27) for CRC, 1.24 (95% CI 1.09-1.41) for colon cancer and 0.99 (95% CI 0.83-1.17) for rectal cancer. Associations were more pronounced in men and not significant in women. The IPS was associated with CRC risk, particularly colon cancer among men; HRs for the highest versus lowest IPS was 1.62 (95% CI 1.31-2.01) for colon cancer overall and 2.11 (95% CI 1.50-2.97) for colon cancer in men. Our study shows that more proinflammatory diets and a more inflammatory profile are associated with higher risk of CRC, principally colon cancer and in men.
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http://dx.doi.org/10.1002/ijc.32870DOI Listing
August 2020

Nutrient-wide association study of 92 foods and nutrients and breast cancer risk.

Breast Cancer Res 2020 01 13;22(1). Epub 2020 Jan 13.

Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.

Background: Several dietary factors have been reported to be associated with risk of breast cancer, but to date, unequivocal evidence only exists for alcohol consumption. We sought to systematically assess the association between intake of 92 foods and nutrients and breast cancer risk using a nutrient-wide association study.

Methods: Using data from 272,098 women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we assessed dietary intake of 92 foods and nutrients estimated by dietary questionnaires. Cox regression was used to quantify the association between each food/nutrient and risk of breast cancer. A false discovery rate (FDR) of 0.05 was used to select the set of foods and nutrients to be replicated in the independent Netherlands Cohort Study (NLCS).

Results: Six foods and nutrients were identified as associated with risk of breast cancer in the EPIC study (10,979 cases). Higher intake of alcohol overall was associated with a higher risk of breast cancer (hazard ratio (HR) for a 1 SD increment in intake = 1.05, 95% CI 1.03-1.07), as was beer/cider intake and wine intake (HRs per 1 SD increment = 1.05, 95% CI 1.03-1.06 and 1.04, 95% CI 1.02-1.06, respectively), whereas higher intakes of fibre, apple/pear, and carbohydrates were associated with a lower risk of breast cancer (HRs per 1 SD increment = 0.96, 95% CI 0.94-0.98; 0.96, 95% CI 0.94-0.99; and 0.96, 95% CI 0.95-0.98, respectively). When evaluated in the NLCS (2368 cases), estimates for each of these foods and nutrients were similar in magnitude and direction, with the exception of beer/cider intake, which was not associated with risk in the NLCS.

Conclusions: Our findings confirm a positive association of alcohol consumption and suggest an inverse association of dietary fibre and possibly fruit intake with breast cancer risk.
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http://dx.doi.org/10.1186/s13058-019-1244-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6958698PMC
January 2020
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