Publications
1358 results found
Bixby H, Bentham J, Zhou B, et al., 2019, Rising rural body-mass index is the main driver of the global obesity epidemic, Nature, Vol: 569, Pages: 260-264, ISSN: 0028-0836
Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities1,2. This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity3,4,5,6. Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017—and more than 80% in some low- and middle-income regions—was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing—and in some countries reversal—of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.
Perduca V, Alexandrov LB, Kelly-Irving M, et al., 2019, Stem cell replication, somatic mutations and role of randomness in the development of cancer, European Journal of Epidemiology, Vol: 34, Pages: 439-445, ISSN: 0393-2990
An intense scientific debate has recently taken place relating to the "bad luck" hypothesis in cancer development, namely that intrinsic random, and therefore unavoidable, mutagenic events would have a predominant role in tumorigenesis. In this article we review the main contributions to this debate and explain the reasons why the claim that cancer is mostly explained by intrinsic random factors is unsupported by data and theoretical models. In support of this, we present an analysis showing that smoking-induced mutations are more predictive of cancer risk than the lifetime number of stem cell cellular divisions.
Donaire-Gonzalez D, Valentin A, van Nunen E, et al., 2019, ExpoApp: An integrated system to assess multiple personal environmental exposures, Environment International, Vol: 126, Pages: 494-503, ISSN: 0160-4120
To assess environmental exposures at the individual level, new assessment methods and tools are required. We developed an exposure assessment system (ExpoApp) for smartphones. ExpoApp integrates: (i) geo-location and accelerometry measurements from a waist attached smartphone, (ii) data from portable monitors, (iii) geographic information systems, and (iv) individual's information. ExpoApp calculates time spent in microenvironments, physical activity level, inhalation rate, and environmental exposures and doses (e.g., green spaces, inhaled ultrafine particles- UFP). We deployed ExpoApp in a panel study of 158 adults from five cities (Amsterdam and Utrecht- the Netherlands, Basel- Switzerland, Norwich- UK, and Torino- Italy) with an UFP monitor. To evaluate ExpoApp, participants also carried a reference accelerometer (ActiGraph) and completed a travel-activity diary (TAD). System reliability and validity of measurements were evaluated by comparing the monitoring failure rate and the agreement on time spent in microenvironments and physical activity with the reference tools. There were only significant failure rate differences between ExpoApp and ActiGraph in Norwich. Agreement on time in microenvironments and physical activity level between ExpoApp and reference tools was 86.6% (86.5–86.7) and 75.7% (71.5–79.4), respectively. ExpoApp estimated that participants inhaled 16.5 × 1010 particles/day of UFP and had almost no contact with green spaces (24% of participants spent ≥30 min/day in green spaces). Participants with more contact with green spaces had higher inhaled dose of UFP, except for the Netherlands, where the relationship was the inverse. ExpoApp is a reliable system and provides accurate individual's measurements, which may help to understand the role of environmental exposures on the origin and course of diseases.
McCrory C, Leahy S, Ribeiro AI, et al., 2019, Maternal educational inequalities in measured body mass index trajectories in three European countries, PAEDIATRIC AND PERINATAL EPIDEMIOLOGY, Vol: 33, Pages: 226-237, ISSN: 0269-5022
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- Citations: 15
Riso L, Kaaks R, Kühn T, et al., 2019, General and abdominal adiposity and the risk of parkinson's disease.A prospective chort study, Parkinsonism and Related Disorders, Vol: 62, Pages: 98-104, ISSN: 1353-8020
IntroductionDue to demographic change, an increase in the frequency of Parkinson's disease (PD) patients is expected in the future and, thus, the identification of modifiable risk factors is urgently needed. We aimed to examine the associations of body mass index (BMI) and waist circumference (WC) with incident PD.MethodsIn 13 of the 23 centers of the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a total of 734 incident cases of PD were identified between 1992 and 2012 with a mean follow-up of 12 years. Cox proportional hazards regression was used to calculate hazard ratios (HR) with 95% confidence intervals (CI). We modelled anthropometric variables as continuous and categorical exposures and performed subgroup analyses by potential effect modifiers including sex and smoking.ResultsWe found no association between BMI, WC and incident PD, neither among men nor among women. Among never and former smokers, BMI and waist circumference were also not associated with PD risk. For male smokers, however, we observed a statistically significant inverse association between BMI and PD risk (HR 0.51, 95%CI: 0.30, 0.84) and the opposite for women, i.e. a significant direct association of BMI (HR 1.79, 95%CI: 1.04, 3.08) and waist circumference (HR 1.64, 95%CI: 1.03, 2.61) with risk of PD.ConclusionOur data revealed no association between excess weight and PD risk but a possible interaction between anthropometry, sex and smoking.
Georgiadis P, Gavriil M, Rantakokko P, et al., 2019, DNA methylation profiling implicates exposure to PCBs in the pathogenesis of B-cell chronic lymphocytic leukemia, Environment International, Vol: 126, Pages: 24-36, ISSN: 0160-4120
OBJECTIVES: To characterize the impact of PCB exposure on DNA methylation in peripheral blood leucocytes and to evaluate the corresponding changes in relation to possible health effects, with a focus on B-cell lymphoma. METHODS: We conducted an epigenome-wide association study on 611 adults free of diagnosed disease, living in Italy and Sweden, in whom we also measured plasma concentrations of 6 PCB congeners, DDE and hexachlorobenzene. RESULTS: We identified 650 CpG sites whose methylation correlates strongly (FDR < 0.01) with plasma concentrations of at least one PCB congener. Stronger effects were observed in males and in Sweden. This epigenetic exposure profile shows extensive and highly statistically significant overlaps with published profiles associated with the risk of future B-cell chronic lymphocytic leukemia (CLL) as well as with clinical CLL (38 and 28 CpG sites, respectively). For all these sites, the methylation changes were in the same direction for increasing exposure and for higher disease risk or clinical disease status, suggesting an etiological link between exposure and CLL. Mediation analysis reinforced the suggestion of a causal link between exposure, changes in DNA methylation and disease. Disease connectivity analysis identified multiple additional diseases associated with differentially methylated genes, including melanoma for which an etiological link with PCB exposure is established, as well as developmental and neurological diseases for which there is corresponding epidemiological evidence. Differentially methylated genes include many homeobox genes, suggesting that PCBs target stem cells. Furthermore, numerous polycomb protein target genes were hypermethylated with increasing exposure, an effect known to constitute an early marker of carcinogenesis. CONCLUSIONS: This study provides mechanistic evidence in support of a link between exposure to PCBs and the etiology of CLL and underlines the utility of omic profiling in the evaluation o
Johansson A, Palli D, Masala G, et al., 2019, Epigenome-wide association study for lifetime estrogen exposure identifies an epigenetic signature associated with breast cancer risk, Clinical Epigenetics, Vol: 11, ISSN: 1868-7083
BackgroundIt is well established that estrogens and other hormonal factors influence breast cancer susceptibility. We hypothesized that a woman’s total lifetime estrogen exposure accumulates changes in DNA methylation, detectable in the blood, which could be used in risk assessment for breast cancer.MethodsAn estimated lifetime estrogen exposure (ELEE) model was defined using epidemiological data from EPIC-Italy (n = 31,864). An epigenome-wide association study (EWAS) of ELEE was performed using existing Illumina HumanMethylation450K Beadchip (HM450K) methylation data obtained from EPIC-Italy blood DNA samples (n = 216). A methylation index (MI) of ELEE based on 31 CpG sites was developed using HM450K data from EPIC-Italy and the Generations Study and evaluated for association with breast cancer risk in an independent dataset from the Generations Study (n = 440 incident breast cancer cases matched to 440 healthy controls) using targeted bisulfite sequencing. Lastly, a meta-analysis was conducted including three additional cohorts, consisting of 1187 case-control pairs.ResultsWe observed an estimated 5% increase in breast cancer risk per 1-year longer ELEE (OR = 1.05, 95% CI 1.04–1.07, P = 3 × 10−12) in EPIC-Italy. The EWAS identified 694 CpG sites associated with ELEE (FDR Q < 0.05). We report a DNA methylation index (MI) associated with breast cancer risk that is validated in the Generations Study targeted bisulfite sequencing data (ORQ4_vs_Q1 = 1.77, 95% CI 1.07–2.93, P = 0.027) and in the meta-analysis (ORQ4_vs_Q1 = 1.43, 95% CI 1.05–2.00, P = 0.024); however, the correlation between the MI and ELEE was not validated across study cohorts.ConclusionWe have identified a blood DNA methylation signature associated with breast cancer risk in this study. Further investigation is required to confirm the inte
Honda K, Katzke VA, Husing A, et al., 2019, CA19-9 and Apolipoprotein-A2 isoforms as detection markers for pancreatic cancer - a prospective evaluation, International Journal of Cancer, Vol: 144, Pages: 1877-1887, ISSN: 0020-7136
Recently, we identified unique processing patterns of apolipoprotein A2 (ApoA2) in patients with pancreatic cancer. This study provides a first prospective evaluation of an ApoA2 isoform (“ApoA2-ATQ/AT”), alone and in combination with carbohydrate antigen 19-9 (CA19-9), as an early detection biomarker for pancreatic cancer.We performed ELISA measurements of CA19-9 and ApoA2-ATQ/AT in 156 patients with pancreatic cancer and 217 matched controls within the European EPIC cohort, using plasma samples collected up to 60 months prior to diagnosis. The detection discrimination statistics were calculated for risk scores by strata of lag-time.For CA19-9, in univariate marker analyses, C-statistics to distinguish future pancreatic cancer patients from cancer-free individuals were 0.80 for plasma taken ≤6 months before diagnosis, and 0.71 for >6-18 months; for ApoA2-ATQ/AT, C-statistics were 0.62, and 0.65, respectively. Joint models based on ApoA2-ATQ/AT plus CA19-9 significantly improved discrimination within >6-18 months (C = 0.74 vs. 0.71 for CA19-9 alone, p = 0.022) and ≤18 months (C = 0.75 vs. 0.74, p = 0.022). At 98% specificity, and for lag times of ≤6, >6-18 or ≤18 months, sensitivities were 57%, 36% and 43% for CA19-9 combined with ApoA2-ATQ/AT, respectively, vs. 50%, 29% and 36% for CA19-9 alone. Compared to CA19-9 alone, the combination of CA19-9 and ApoA2-ATQ/AT may improve detection of pancreatic cancer up to 18 months prior to diagnosis under usual care, and may provide a useful first measure for pancreatic cancer detection prior to imaging.
Fiorito G, McCrory C, Robinson O, et al., 2019, Socioeconomic position, lifestyle habits and biomarkers of epigenetic aging: a multi-cohort analysis, Aging, Vol: 11, Pages: 2045-2070, ISSN: 1945-4589
Differences in health status by socioeconomic position (SEP) tend to be more evident at older ages, suggesting the involvement of a biological mechanism responsive to the accumulation of deleterious exposures across the lifespan. DNA methylation (DNAm) hasbeen proposed as a biomarker of biological aging that conserves memory of endogenous and exogenous stress during life. We examined the association of education level, as an indicator of SEP, and lifestyle-related variables with four biomarkers of age-dependent DNAm dysregulation: the total number of stochastic epigenetic mutations (SEMs) and three epigenetic clocks (Horvath, Hannum and Levine), in 18 cohorts spanning 12 countries. The four biological aging biomarkers were associated with education and different sets of risk factors independently,and themagnitude of the effectsdiffereddepending on the biomarker and the predictor. On average, the effect of low education on epigenetic aging was comparable with those of other lifestyle-related risk factors (obesity, alcohol intake), with the exception ofsmoking, which hada significantly stronger effect. Our study shows that low education is an independent predictor of accelerated biological (epigenetic) aging and that epigenetic clocks appear to be good candidates for disentangling the biological pathways underlying social inequalities in healthy aging and longevity.
Reimann B, Janssen BG, Alfano R, et al., 2019, The cord blood insulin and mitochondrial DNA content related methylome, Frontiers in Genetics, Vol: 10, ISSN: 1664-8021
Mitochondrial dysfunction seems to play a key role in the etiology of insulin resistance. At birth, a link has already been established between mitochondrial DNA (mtDNA) content and insulin levels in cord blood. In this study, we explore shared epigenetic mechanisms of the association between mtDNA content and insulin levels, supporting the developmental origins of this link. First, the association between cord blood insulin and mtDNA content in 882 newborns of the ENVIRONAGE birth cohort was assessed. Cord blood mtDNA content was established via qPCR, while cord blood levels of insulin were determined using electrochemiluminescence immunoassays. Then the cord blood DNA methylome and transcriptome were determined in 179 newborns, using the human 450K methylation Illumina and Agilent Whole Human Genome 8 × 60 K microarrays, respectively. Subsequently, we performed an epigenome-wide association study (EWAS) adjusted for different maternal and neonatal variables. Afterward, we focused on the 20 strongest associations based on p-values to assign transcriptomic correlates and allocate corresponding pathways employing the R packages ReactomePA and RDAVIDWebService. On the regional level, we examined differential methylation using the DMRcate and Bumphunter packages in R. Cord blood mtDNA content and insulin were significantly correlated (r = 0.074, p = 0.028), still showing a trend after additional adjustment for maternal and neonatal variables (p = 0.062). We found an overlap of 33 pathways which were in common between the association with cord blood mtDNA content and insulin levels, including pathways of neurodevelopment, histone modification, cytochromes P450 (CYP)-metabolism, and biological aging. We further identified a DMR annotated to Repulsive Guidance Molecule BMP Co-Receptor A (RGMA) linked to cord blood insulin as well as mtDNA content. Metabolic variation in early life represented by neonatal insulin levels and mtDNA content might reflect or accommodate
Park JY, Bueno-de-Mesquita HB, Ferrari P, et al., 2019, Dietary folate intake and pancreatic cancer risk: results from the European Prospective Investigation into Cancer and Nutrition, International Journal of Cancer, Vol: 144, Pages: 1511-1521, ISSN: 0020-7136
Pancreatic cancer (PC) has an exceptionally low survival rate and primary prevention strategies are limited. Folate plays an important role in one-carbon metabolism and has been associated with the risk of several cancers, but not consistently with PC risk. We aimed to investigate the association between dietary folate intake and PC risk, using the standardised folate database across 10 European countries. A total of 477,206 participants were followed up for 11 years, during which 865 incident primary PC cases were recorded. Folate intake was energy-adjusted using the residual method. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. In multivariable analyses stratified by age, sex, study centre and adjusted for energy intake, smoking status, BMI, educational level, diabetes status, supplement use and dietary fibre intake, we found no significant association between folate intake and PC risk: the HR of PC risk for those in the highest quartile of folate intake (≥353 μg/d) compared with the lowest (<241 μg/d) was 0.81 (95% CI: 0.51, 1.31; Ptrend = 0.38). In current smokers, a positive trend was observed in PC risk across folate quartiles (HR=4.42 (95% CI: 1.05, 18.62) for ≥353 μg/d vs. <241 μg/d, Ptrend = 0.01). Nonetheless, there was no significant interaction between smoking and dietary folate intake (Pinteraction = 0.99). We found no association between dietary folate intake and PC risk in this large European study.
Sciannameo V, Carta A, d'Errico A, et al., 2019, New insights on occupational exposure and bladder cancer risk: a pooled analysis of two Italian case-control studies, INTERNATIONAL ARCHIVES OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH, Vol: 92, Pages: 347-359, ISSN: 0340-0131
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- Citations: 4
Solans M, Benavente Y, Saez M, et al., 2019, Inflammatory potential of diet and risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition, European Journal of Nutrition, Vol: 59, Pages: 813-823, ISSN: 0044-264X
INTRODUCTION: Chronic inflammation plays a critical role in lymphomagenesis and several dietary factors seem to be involved its regulation. The aim of the current study was to assess the association between the inflammatory potential of the diet and the risk of lymphoma and its subtypes in the European Investigation into Cancer and Nutrition (EPIC) study. METHODS: The analysis included 476,160 subjects with an average follow-up of 13.9 years, during which 3,136 lymphomas (135 Hodgkin lymphoma (HL), 2606 non-Hodgkin lymphoma (NHL) and 395 NOS) were identified. The dietary inflammatory potential was assessed by means of an inflammatory score of the diet (ISD), calculated using 28 dietary components and their corresponding inflammatory weights. The association between the ISD and lymphoma risk was estimated by hazard ratios (HR) and 95% confidence intervals (CI) calculated by multivariable Cox regression models adjusted for potential confounders. RESULTS: The ISD was not associated with overall lymphoma risk. Among lymphoma subtypes, a positive association between the ISD and mature B-cell NHL (HR for a 1-SD increase: 1.07 (95% CI 1.01; 1.14), p trend = 0.03) was observed. No statistically significant association was found among other subtypes. However, albeit with smaller number of cases, a suggestive association was observed for HL (HR for a 1-SD increase = 1.22 (95% CI 0.94; 1.57), p trend 0.13). CONCLUSIONS: Our findings suggested that a high ISD score, reflecting a pro-inflammatory diet, was modestly positively associated with the risk of B-cell lymphoma subtypes. Further large prospective studies on low-grade inflammation induced by diet are warranted to confirm these findings.
Smith T, Muller D, Moons K, et al., 2019, Comparison of prognostic models to predict the occurrence of colorectal cancer in asymptomatic individuals: A systematic literature review and external validation in the EPIC and UK Biobank prospective cohort studies, Gut, Vol: 68, Pages: 672-683, ISSN: 0017-5749
ObjectiveTo systematically identify and validate published colorectal cancer risk prediction models that do not require invasive testing in two large population-based prospective cohorts.DesignModels were identified through an update of a published systematic review and validated in the European Prospective Investigation into Cancer and Nutrition (EPIC) and the UK Biobank. The performance of the models to predict the occurrence of colorectal cancer within 5 or 10 years after study enrolment was assessed by discrimination (C-statistic) and calibration (plots of observed versus predicted probability).ResultsThe systematic review and its update identified 16 models from 8 publications (8 colorectal, 5 colon and 3 rectal). The number of participants included in each model validation ranged from 41,587 to 396,515, and the number of cases from 115 to 1,781. Eligible and ineligible participants across the models were largely comparable. Calibration of the models, where assessable, was very good and further improved by recalibration. The C-statistics of the models were largely similar between validation cohorts with the highest values achieved being 0.70 (95%CI 0.68-0.72) in the UK Biobank and 0.71 (0.67-0.74) in EPIC. ConclusionSeveral of these non-invasive models exhibited good calibration and discrimination within both external validation populations and are therefore potentially suitable candidates for the facilitation of risk stratification in population-based colorectal screening programmes. Future work should both evaluate this potential, through modelling and impact studies, and ascertain if further enhancement in their performance can be obtained.
Wild CP, Espina C, Bauld L, et al., 2019, Cancer prevention Europe, Molecular Oncology, Vol: 13, Pages: 528-534, ISSN: 1878-0261
The case for cancer prevention in Europe is the same as for all other parts of the world. The number of cancers is increasing, driven by demographic change and evolution in the exposure to risk factors, while the cost of treating patients is likewise spiralling. Estimations suggest that around 40% of cancers in Europe could be prevented if current understanding of risk and protective factors was translated into effective primary prevention, with further reductions in cancer incidence and mortality by screening, other approaches to early detection, and potentially medical prevention. However, the infrastructure for cancer prevention tends to be fragmented between and within different countries in Europe. This lack of a coordinated approach recently led to the foundation of Cancer Prevention Europe (Forman et al., 2018), a collaborative network with the main aims of strengthening cancer prevention in Europe by increasing awareness of the needs, the associated required resources and reducing inequalities in access to cancer prevention across Europe. This article showcases the need for strengthening cancer prevention and introduces the objectives of Cancer Prevention Europe and its foreseen future role in reducing the European cancer burden.
Vineis P, 2019, What is the exposome and how it can help research on air pollution, Emission Control Science and Technology, Vol: 5, Pages: 31-36, ISSN: 2199-3629
The concept of “exposome” has been introduced to allow an empowerment of environmental research, by improving measurements of external stressors and of internal biological changes, the latter taking advantage of advancements in high-throughput technologies called “omics.” Here, I discuss the application of the exposome concept and techniques to the field of air pollution. I address some open issues in air pollution science, such as the effects of components in a mixture, low doses, biological pathways, and a meaningful interpretation of omic findings in the context of “hallmarks” of disease. The exposome may represent the next frontier for the regulation of low-dose environmental contaminants.
Gaudet MM, Deubler EL, Kelly RS, et al., 2019, Blood levels of cadmium and lead in relation to breast cancer risk in three prospective cohorts, International Journal of Cancer, Vol: 144, Pages: 1010-1016, ISSN: 0020-7136
Cadmium and lead have been classified as carcinogens by the International Agency for Research on Cancer. However, their associations with breast cancer risk are unknown despite their persistence in the environment and ubiquitous human exposure. We examined associations of circulating levels of cadmium and lead with breast cancer risk in three case-control studies nested within the Cancer Prevention Study-II (CPS-II) LifeLink Cohort, European Prospective Investigation into Cancer and Nutrition - Italy (EPIC-Italy), and the Northern Sweden Health and Disease Study (NSHDS) cohorts. Metal levels were measured in stored erythrocytes from 1,435 cases and 1,433 controls using inductively coupled plasma-mass spectrometry. Summary relative risks (RR) and 95% confidence intervals (CI) were calculated using random-effects models with each study result weighted by the within- and between-study variances. I2 values were calculated to estimate proportion of between study variation. Using common cut-points, cadmium levels were not associated with breast cancer risk in the CPS-II cohort (continuous RR=1.01, 95% CI 0.76 - 1.34), but were inversely associated with risk in the EPIC- Italy (continuous RR=0.80, 95% CI 0.61 - 1.03) and NSHDS cohorts (continuous RR=0.73, 95% CI 0.54 - 0.97). The inverse association was also evident in the meta-analysis (continuous RR=0.84, 95% CI 0.69 - 1.01) with low between-study heterogeneity. Large differences in lead level distributions precluded a meta-analysis of their association with breast cancer risk; no associations were found in the three studies. Adult cadmium and lead levels were not associated with higher risk of breast cancer in our large meta-analysis.
Jeong A, Imboden M, Ghantous A, et al., 2019, DNA methylation in inflammatory pathways modifies the association between BMI and adult-onset non-atopic asthma, International Journal of Environmental Research and Public Health, Vol: 16, ISSN: 1660-4601
A high body mass (BMI) index has repeatedly been associated with non-atopic asthma, but the biological mechanism linking obesity to asthma is still poorly understood. We aimed to test the hypothesis that inflammation and/or innate immunity plays a role in the obesity-asthma link. DNA methylome was measured in blood samples of 61 non-atopic participants with asthma and 146 non-atopic participants without asthma (non-smokers for at least 10 years) taking part in the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) study. Modification by DNA methylation of the association of BMI or BMI change over 10 years with adult-onset asthma was examined at each CpG site and differentially methylated region. Pathway enrichment tests were conducted for genes in a priori curated inflammatory pathways and the NLRP3-IL1B-IL17 axis. The latter was chosen on the basis of previous work in mice. Inflammatory pathways including glucocorticoid/PPAR signaling (p = 0.0023), MAPK signaling (p = 0.013), NF-κB signaling (p = 0.031), and PI3K/AKT signaling (p = 0.031) were enriched for the effect modification of BMI, while NLRP3-IL1B-IL17 axis was enriched for the effect modification of BMI change over 10 years (p = 0.046). DNA methylation measured in peripheral blood is consistent with inflammation as a link between BMI and adult-onset asthma and with the NLRP3-IL1B-IL17 axis as a link between BMI change over 10 years and adult-onset asthma in non-atopic participants.
Berger E, Castagne R, Chadeau M, et al., 2019, Multi-cohort study identifies social determinants of systemic inflammation over the life course, Nature Communications, Vol: 10, ISSN: 2041-1723
Chronic inflammation has been proposed as having a prominent role in the construction of social inequalities in health. Disentangling the effects of early life and adulthood social disadvantage on inflammation is key in elucidating biological mechanisms underlying socioeconomic disparities. Here we explore the relationship between socioeconomic position (SEP) across the life course and inflammation (as measured by CRP levels) in up to 23,008 participants from six European cohort studies from three countries conducted between 1958 and 2013. We find a consistent inverse association between SEP and CRP across cohorts, where participants with a less advantaged SEP have higher levels of inflammation. Educational attainment is most strongly related to inflammation, after adjusting for health behaviours, body mass index and later-in-life SEP. These findings suggest socioeconomic disadvantage in young adulthood is independently associated with later life inflammation calling for further studies of the pathways operating through educational processes.
Chadeau M, van Veldhoven C, Kiss A, et al., 2019, Impact of short-term traffic-related air pollution on the metabolome – results from two metabolome-wide experimental studies, Environment International, Vol: 123, Pages: 124-131, ISSN: 0160-4120
Exposure to traffic-related air pollution (TRAP) has been associated with adverse health outcomes but underlying biological mechanisms remain poorly understood. Two randomized crossover trials were used here, the Oxford Street II (London) and the TAPAS II (Barcelona) studies, where volunteers were allocated to high or low air pollution exposures. The two locations represent different exposure scenarios, with Oxford Street characterized by diesel vehicles and Barcelona by normal mixed urban traffic. Levels of five and four pollutants were measured, respectively, using personal exposure monitoring devices. Serum samples were used for metabolomic profiling. The association between TRAP and levels of each metabolic feature was assessed. All pollutant levels were significantly higher at the high pollution sites. 29 and 77 metabolic features were associated with at least one pollutant in the Oxford Street II and TAPAS II studies, respectively, which related to 17 and 30 metabolic compounds. Little overlap was observed across pollutants for metabolic features, suggesting that different pollutants may affect levels of different metabolic features. After observing the annotated compounds, the main pathway suggested in Oxford Street II in association with NO2 was the acyl-carnitine pathway, previously found to be associated with cardio-respiratory disease. No overlap was found between the metabolic features identified in the two studies.
Gasull M, Pumarega J, Kiviranta H, et al., 2019, Methodological issues in a prospective study on plasma concentrations of persistent organic pollutants and pancreatic cancer risk within the EPIC cohort, Environmental Research, Vol: 169, Pages: 417-433, ISSN: 0013-9351
BACKGROUND: The use of biomarkers of environmental exposure to explore new risk factors for pancreatic cancer presents clinical, logistic, and methodological challenges that are also relevant in research on other complex diseases. OBJECTIVES: First, to summarize the main design features of a prospective case-control study -nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort- on plasma concentrations of persistent organic pollutants (POPs) and pancreatic cancer risk. And second, to assess the main methodological challenges posed by associations among characteristics and habits of study participants, fasting status, time from blood draw to cancer diagnosis, disease progression bias, basis of cancer diagnosis, and plasma concentrations of lipids and POPs. Results from etiologic analyses on POPs and pancreatic cancer risk, and other analyses, will be reported in future articles. METHODS: Study subjects were 1533 participants (513 cases and 1020 controls matched by study centre, sex, age at blood collection, date and time of blood collection, and fasting status) enrolled between 1992 and 2000. Plasma concentrations of 22 POPs were measured by gas chromatography - triple quadrupole mass spectrometry (GC-MS/MS). To estimate the magnitude of the associations we calculated multivariate-adjusted odds ratios by unconditional logistic regression, and adjusted geometric means by General Linear Regression Models. RESULTS: There were differences among countries in subjects' characteristics (as age, gender, smoking, lipid and POP concentrations), and in study characteristics (as time from blood collection to index date, year of last follow-up, length of follow-up, basis of cancer diagnosis, and fasting status). Adjusting for centre and time of blood collection, no factors were significantly associated with fasting status. Plasma concentrations of lipids were related to age, body mass index, fasting, country, and smoking. We detected and quan
Chadeau M, Alfano R, Guida F, et al., 2019, Socioeconomic position during pregnancy and DNA methylation signatures at three stages across the early life: epigenome-wide association studies in the ALSPAC birth cohort, International Journal of Epidemiology, Vol: 48, ISSN: 1464-3685
BackgroundSocioeconomic experiences are recognized determinants of health, and recent work has shown that social disadvantages in early life may induce sustained biological changes at molecular level that are detectable later in life. However, the dynamics and persistence of biological embedding of socioeconomic position (SEP) remains vastly unexplored.MethodsUsing the data from the ALSPAC birth cohort, we performed epigenome-wide association studies of DNA methylation changes at three life stages (birth, n = 914; childhood at mean age 7.5 years, n = 973; and adolescence at mean age 15.5 years, n = 974), measured using the Illumina HumanMethylation450 Beadchip, in relation to pregnancy SEP indicators (maternal and paternal education and occupation).ResultsAcross the four early life SEP metrics investigated, only maternal education was associated with methylation levels at birth, and four CpGs mapped to SULF1, GLB1L2 and RPUSD1 genes were identified [false discovery rate (FDR)-corrected P-value <0.05]. No epigenetic signature was found associated with maternal education in child samples, but methylation levels at 20 CpG loci were found significantly associated with maternal education in adolescence. Although no overlap was found between the differentially methylated CpG sites at different ages, we identified two CpG sites at birth and during adolescence which are 219 bp apart in the SULF1 gene that encodes an heparan sulphatase involved in modulation of signalling pathways. Using data from an independent birth cohort, the ENVIRONAGE cohort, we were not able to replicate these findings.ConclusionsTaken together, our results suggest that parental SEP, and particularly maternal education, may influence the offspring’s methylome at birth and adolescence.
Brenner DR, Fehringer G, Zhang Z-F, et al., 2019, Alcohol consumption and lung cancer risk: A pooled analysis from the International Lung Cancer Consortium and the SYNERGY study, CANCER EPIDEMIOLOGY, Vol: 58, Pages: 25-32, ISSN: 1877-7821
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Layte R, McCrory C, Cheallaigh CN, et al., 2019, A Comparative Analysis of the Status Anxiety Hypothesis of Socio-economic Inequalities in Health Based on 18,349 individuals in Four Countries and Five Cohort Studies, SCIENTIFIC REPORTS, Vol: 9, ISSN: 2045-2322
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- Citations: 20
Demetriou CA, Van Veldhoven K, Relton C, et al., 2019, Gaps in knowledge and missing evidence in the role of DNA methylation in biological embedding, Handbook of Nutrition, Diet, and Epigenetics, Pages: 1177-1192, ISBN: 9783319555294
The thrifty phenotype hypothesis - the theory that under- or malnutrition during gestation could permanently influence the body's structure and function contributing to adult disease - has then been closely linked with biological embedding, the process through which external exposures "get under the skin" to influence human biological processes. Biological embedding has been hypothesized to occur through three different processes which may often coexist: latent effects, cumulative effects, and pathway effects. Irrespective of the exact mechanism, in order for biological embedding to occur, responses to an environmental signal need to be stage dependent, heritable, and persistent. Such phenotypic effects can be explained by epigenetic modifications imposed by environmental signals, which are themselves heritable, time dependent, and tissue as well as sex specific. DNA methylation is the epigenetic mechanism that has been most extensively studied in this context. The synthesis of current research relating to the biological embodiment of early-life exposures through DNA methylation provides some support to the involvement of DNA methylation in biological embedding and provides evidence for a mechanism through which early-life exposures can affect disease risk later in life. However, there still remain several gaps in knowledge which are discussed in this chapter. In order to generate evidence that will strongly support and further elucidate the role of DNA methylation in biological embedding of earlylife exposures, these gaps need to be addressed in more and better designed studies.
Demetriou CA, Van Veldhoven K, Relton C, et al., 2019, Socioeconomics, obesity, and early-life nutrition on the role of DNA methylation in biological embedding, Handbook of Nutrition, Diet, and Epigenetics, Pages: 125-143, ISBN: 9783319555294
Early-life socioeconomic conditions, childhood obesity, and early-life nutrition are factors that have been associated with chronic disease in adult life. The synthesis of current research relating to the biological embodiment of earlylife exposures through DNA methylation provides some support to the involvement of DNA methylation in biological embedding and provides evidence for a mechanism through which early-life exposures can affect disease risk later in life. More specifically, several studies on early-life socioeconomic conditions, childhood overweight/obesity, and early-life nutrition show DNA methylation effects that can, in some cases, persist for years after the exposure. The results of these studies are reviewed here. This review highlights the plethora of proxies used for these exposures; the small differences observed in methylation, questioning their biological significance; and the lack of clarity regarding the direction and/or the size of some of the effects. In addition, and perhaps most importantly, publication bias cannot be ruled out, and the lack of replication of these results, especially given the lack of overlap between target regions, requires that these results are interpreted cautiously.
Gulliver J, Chen Y, Fuller G, et al., 2019, Do ultrafine particles confound studies on noise and cardiovascular disease?, Pages: 3040-3047, ISSN: 2226-7808
Ultrafine particles (UFP) are emitted by both jet engine aircraft and road traffic and may potentially confound associations between noise and health outcomes. However, neither UFP or noise are routinely measured resulting in a lack of understanding of their relationship. We conducted repeated short-term measurements with portable sensors to assess the correlation between noise and UFP number concentrations (PNC) for aircraft and road traffic. Noise and PNC were measured contemporaneously for 30-minutes at 160 sites (repeated three times at a range of site types) in Norwich, a medium size city in the east of England, and repeatedly up to 71 times per site at nine sites (501 in total) around Gatwick airport. In Combining all measurements at Gatwick Airport the correlation was very weak (U = 0.11). Strongest correlations were moderate (|>0.4-0.6|) at a residential site 1.3 km north of the runway and a site 0.6 km south of the runway. The correlation between noise and PNC in Norwich was overall moderate (U = 0.52) and weak (U <0.4) for roadside sites (n = 55) and urban background sites (n = 90) respectively. Results suggest that PNC are unlikely to be a major confounder in epidemiological studies of aircraft or road noise and cardiovascular disease.
Cugliari G, Benevenuta S, Guarrera S, et al., 2019, Improving the prediction of cardiovascular risk with machine-learning and DNA methylation data, 16th IEEE International Conference on Computational Intelligence in Bioinformatics and Computational Biology (IEEE CIBCB), Publisher: IEEE, Pages: 39-42
Downward GS, van Nunen EJHM, Kerckhoffs J, et al., 2018, Long-Term Exposure to Ultrafine Particles and Incidence of Cardiovascular and Cerebrovascular Disease in a Prospective Study of a Dutch Cohort, ENVIRONMENTAL HEALTH PERSPECTIVES, Vol: 126, ISSN: 0091-6765
Chadeau M, Campanella G, Gunter MJ, et al., 2018, Epigenome-wide association study of adiposity and future risk of obesity-related diseases, International Journal of Obesity, Vol: 42, Pages: 2022-2035, ISSN: 0307-0565
BackgroundObesity is an established risk factor for several common chronic diseases such as breast and colorectal cancer, metabolic and cardiovascular diseases; however, the biological basis for these relationships is not fully understood. To explore the association of obesity with these conditions, we investigated peripheral blood leucocyte (PBL) DNA methylation markers for adiposity and their contribution to risk of incident breast and colorectal cancer and myocardial infarction.MethodsDNA methylation profiles (Illumina Infinium® HumanMethylation450 BeadChip) from 1941 individuals from four population-based European cohorts were analysed in relation to body mass index, waist circumference, waist-hip and waist-height ratio within a meta-analytical framework. In a subset of these individuals, data on genome-wide gene expression level, biomarkers of glucose and lipid metabolism were also available. Validation of methylation markers associated with all adiposity measures was performed in 358 individuals. Finally, we investigated the association of obesity-related methylation marks with breast, colorectal cancer and myocardial infarction within relevant subsets of the discovery population.ResultsWe identified 40 CpG loci with methylation levels associated with at least one adiposity measure. Of these, one CpG locus (cg06500161) in ABCG1 was associated with all four adiposity measures (P = 9.07×10−8 to 3.27×10−18) and lower transcriptional activity of the full-length isoform of ABCG1 (P = 6.00×10−7), higher triglyceride levels (P = 5.37×10−9) and higher triglycerides-to-HDL cholesterol ratio (P = 1.03×10−10). Of the 40 informative and obesity-related CpG loci, two (in IL2RB and FGF18) were significantly associated with colorectal cancer (inversely, P < 1.6×10−3) and one intergenic locus on chromosome 1 was inversely associa
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