0000000000925439
AUTHOR
Manolis Kogevinas
Drinking water disinfection by-products, genetic polymorphisms, and birth outcomes in a european mother-child cohort study
Background: We examined the association between exposure during pregnancy to trihalomethanes, the most common water disinfection by-products, and birth outcomes in a European cohort study (Health Impacts of Long-Term Exposure to Disinfection By-Products in Drinking Water). We took into account exposure through different water uses, measures of water toxicity, and genetic susceptibility. Methods: We enrolled 14,005 mothers (2002-2010) and their children from France, Greece, Lithuania, Spain, and the UK. Information on lifestyle-and water-related activities was recorded. We ascertained residential concentrations of trihalomethanes through regulatory records and ad hoc sampling campaigns and e…
Mechanisms of the Development of Allergy (MeDALL) : Introducing novel concepts in allergy phenotypes
Asthma, rhinitis, and eczema are complex diseases with multiple genetic and environmental factors interlinked through IgE-associated and non–IgE-associated mechanisms. Mechanisms of the Development of ALLergy (MeDALL; EU FP7-CP-IP; project no: 261357; 2010-2015) studied the complex links of allergic diseases at the clinical and mechanistic levels by linking epidemiologic, clinical, and mechanistic research, including in vivo and in vitro models. MeDALL integrated 14 European birth cohorts, including 44,010 participants and 160 cohort follow-ups between pregnancy and age 20 years. Thirteen thousand children were prospectively followed after puberty by using a newly standardized MeDALL Core Q…
Exposure to trihalomethanes through different water uses and birth weight, small for gestational age, and preterm delivery in Spain
Background: Evidence associating exposure to water disinfection by-products with reduced birth weight and altered duration of gestation remains inconclusive. Objective: We assessed exposure to trihalomethanes (THMs) during pregnancy through different water uses and evaluated the association with birth weight, small for gestational age (SGA), low birth weight (LBW), and preterm delivery. Methods: Mother–child cohorts set up in five Spanish areas during the years 2000–2008 contributed data on water ingestion, showering, bathing, and swimming in pools. We ascertained residential THM levels during pregnancy periods through ad hoc sampling campaigns (828 measurements) and regulatory data (264 me…
Occupational Exposure to Endocrine-Disrupting Chemicals and Birth Weight and Length of Gestation: A European Meta-Analysis
BACKGROUND: Women of reproductive age can be exposed to endocrine-disrupting chemicals (EDCs) at work, and exposure to EDCs in pregnancy may affect fetal growth. OBJECTIVES: We assessed whether maternal occupational exposure to EDCs during pregnancy as classified by application of a job exposure matrix was associated with birth weight, term low birth weight (LBW), length of gestation, and preterm delivery. METHODS: Using individual participant data from 133,957 mother-child pairs in 13 European cohorts spanning births from 1994 through 2011, we linked maternal job titles with exposure to 10 EDC groups as assessed through a job exposure matrix. For each group, we combined the two levels of e…
Does early onset asthma increase childhood obesity risk? A pooled analysis of 16 European cohorts
The parallel epidemics of childhood asthma and obesity over the past few decades have spurred research into obesity as a risk factor for asthma. However, little is known regarding the role of asthma in obesity incidence. We examined whether early-onset asthma and related phenotypes are associated with the risk of developing obesity in childhood.This study includes 21 130 children born from 1990 to 2008 in Denmark, France, Germany, Greece, Italy, The Netherlands, Spain, Sweden and the UK. We followed non-obese children at 3-4 years of age for incident obesity up to 8 years of age. Physician-diagnosed asthma, wheezing and allergic rhinitis were assessed up to 3-4 years of age.Children with ph…
P021 Heat working environment and risk of breast, chronic lymphocytic leukaemia, colorectal, prostate, and stomach cancer in the MCC-spain case control study
Occupational exposure to heat can affect the absorption of carcinogenic chemicals into the body, and the metabolism of sexual hormones. We explored the association between occupational exposure to heat and breast, chronic lymphocytic leukaemia, colorectal, prostate, and stomach cancer in the MCC-Spain population based case-control study. Methods The analyses were based on 3047 controls, and 1499 breast, 1539 colorectal, 332 LLC, 1070 prostate, and 382 stomach cancer cases. Heat working environment from either natural or artificial sources was assessed with the MatEmEsp job-exposure matrix. Logistic regression models accounting for education, sex, geographic area, BMI (colorectal, prostate),…
Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors
AbstractBirth weight (BW) variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. These associations have been proposed to reflect the lifelong consequences of an adverse intrauterine environment. In earlier work, we demonstrated that much of the negative correlation between BW and adult cardio-metabolic traits could instead be attributable to shared genetic effects. However, that work and other previous studies did not systematically distinguish the direct effects of an individual’s own genotype on BW and subsequent disease risk from indirect effects of their mother’s correlated genoty…
P056 Occupational exposure to metals and risk of breast, chronic lymphocytic leukaemia, colorectal, prostate, and stomach cancer in the MCC-spain case control study
Arsenic, cadmium, chromium, and nickel are classified by IARC as human carcinogens (Group 1), while lead as a probable/possible carcinogen to humans (Group 2A). We explored associations between occupational exposure to metals and breast, chronic lymphocytic leukaemia (CLL), colorectal, prostate, and stomach cancer in the MCC-Spain population based case-control study. Methods The analyses were based on 3047 controls, and 1499 breast, 1539 colorectal, 332 CLL, 1070 prostate, and 382 stomach cancer cases. Occupational exposure to arsenic, cadmium, chromium, iron, lead and nickel was assessed using the MatEmEsp job-exposure matrix. Logistic regression models accounting for education, sex, geogr…
Acetaminophen Use During Pregnancy: Effects on Risk for Congenital Abnormalities
Udgivelsesdato: 2008-Feb OBJECTIVE: We evaluated if acetaminophen, one of the most frequently used drugs among pregnant women is associated with an increased prevalence of congenital abnormalities. STUDY DESIGN: We selected 88,142 pregnant women and their liveborn singletons from the Danish National Birth Cohort who had information on acetaminophen use during the first trimester of pregnancy. We used the National Hospital Registry to identify 3784 (4.3%) children from the cohort diagnosed with 5847 congenital abnormalities. RESULTS: Children exposed to acetaminophen during the first trimester of pregnancy (n = 26,424) did not have an increased prevalence of congenital abnormalities (hazard …
Occupational Heat Exposure and Breast Cancer Risk in the MCC-Spain Study.
Background: Mechanisms linking occupational heat exposure with chronic diseases have been proposed. However, evidence on occupational heat exposure and cancer risk is limited. Methods: We evaluated occupational heat exposure and female breast cancer risk in a large Spanish case-control study. We enrolled 1,738 breast cancer cases and 1,910 frequency-matched population controls. A Spanish job exposure matrix, MatEmEsp, was used to assign estimates of the proportion of workers exposed (P greater than or equal to 25% for at least one year) and work time with heat stress (wet bulb globe temperature ISO 7243) for each occupation. We used three exposure indices: ever vs. never exposed, lifetime c…
Occupational exposure to immunologically active agents and risk for lymphoma: The European Epilymph case-control study
Objectives: Allergies and asthma may be protective for the development of lymphoma. We evaluated whether occupational allergens that provoke immune reactivity and asthma through an IgE-mediated pathway are protective for lymphoma. Methods: The Epilymph study includes histologically or cytologically confirmed Hodgkin, B-cell, and T-cell lymphoma cases from six European countries (Spain, France, Germany, Italy, Ireland, and Czech Republic) recruited in 1998-2004. Controls were frequency matched to cases by age, gender, and study centre. Lifetime occupational exposure to seven high molecular weight (HMW) agents was evaluated through an asthma-specific job-exposure matrix. 2205 lymphoma cases a…
Severe Chronic Allergic (and Related) Diseases: A Uniform Approach – A MeDALL – GA<sup>2</sup>LEN – ARIA Position Paper
Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow-up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in …
DNA methylation in childhood asthma
Background: DNA methylation profiles associated with childhood asthma might provide novel insights into disease pathogenesis. We did an epigenome-wide association study to assess methylation profiles associated with childhood asthma. Methods: We did a large-scale epigenome-wide association study (EWAS) within the Mechanisms of the Development of ALLergy (MeDALL) project. We examined epigenome-wide methylation using Illumina Infinium Human Methylation450 BeadChips (450K) in whole blood in 207 children with asthma and 610 controls at age 4–5 years, and 185 children with asthma and 546 controls at age 8 years using a cross-sectional case-control design. After identification of differentially m…
Smoking and Helicobacter pylori infection: an individual participant pooled analysis (Stomach Cancer Pooling- StoP Project)
Smoking has been associated with acquisition and increased persistence of Helicobacter pylori infection, as well as with lower effectiveness of its eradication. A greater prevalence of infection among smokers could contribute to the increased risk for gastric cancer. We aimed to estimate the association between smoking and seropositivity to H. pylori through an individual participant data pooled analysis using controls from 14 case- control studies participating in the Stomach Cancer Pooling Project. Summary odds ratios and prevalence ratios (PRs), adjusted for age, sex and social class, and the corresponding 95% confidence intervals (CIs) were estimated through random-effects meta-analysis…
Influence of fetal glutathione S-transferase copy number variants on adverse reproductive outcomes
A nested case-control association study was designed to investigate the influence of maternal and fetal copy number variants (CNVs) on reproductive outcomes. Genotypes of ten CNVs encompassing GST and CYP genes were assessed. Significant associations were only found for child CNV genotypes. In particular, the child GSTM1 insertion allele was associated with prematurity protection (odds ratio, 95% CI: 0.67, 0.51-0.89; P < 0.01), whereas the child GSTT2B insertion allele was associated with an increased risk of being small for gestational age (odds ratio, 95% CI: 1.33, 1.07-1.67; P = 0.01). The study highlights the role of the fetal genome in prenatal development and also the need to analyse …
Air Pollution During Pregnancy and Childhood Cognitive and Psychomotor Development: Six European Birth Cohorts
Background: Accumulating evidence from laboratory animal and human studies suggests that air pollution exposure during pregnancy affects cognitive and psychomotor development in childhood. Methods: We analyzed data from 6 European population-based birth cohorts-GENERATI ON R (The Netherlands), DUISBURG (Germany), EDEN (France), GASPII (Italy), RHEA (Greece), and INMA (Spain)-that recruited mother-infant pairs from 1997 to 2008. Air pollution levels-nitrogen oxides (NO2, NOx) in all regions and particulate matter (PM) with diameters of <2.5, <10, and 2.5-10 mu m (PM2.5, PM10, and PMcoarse, respectively) and PM2.5 absorbance in a subgroup-at birth addresses were estimated by land-use regressi…
Associations between air pollution and pediatric eczema, rhinoconjunctivitis and asthma: A meta-analysis of European birth cohorts
Background: Uncertainly continues to exist regarding the role of air pollution on pediatric asthma and allergic conditions, especially as air pollution levels have started to decrease in recent decades. Objective: We examined associations of long-term air pollution levels at the home address with pediatric eczema, rhinoconjunctivitis and asthma prevalences in five birth cohorts (BIB, EDEN, GASPII, RHEA and INMA) from seven areas in five European countries. Methods: Current eczema, rhinoconjunctivitis and asthma were assessed in children aged four (N = 6527) and eight years (N = 2489). A multi-morbidity outcome (≥2 conditions versus none) was also defined. Individual outdoor levels of nitrog…
Fish and seafood consumption during pregnancy and the risk of asthma and allergic rhinitis in childhood
Background: It has been suggested that prenatal exposure to n-3 long-chain fatty acids protects against asthma and other allergy-related diseases later in childhood. The extent to which fish intake in pregnancy protects against child asthma and rhinitis symptoms remains unclear. We aimed to assess whether fish and seafood consumption in pregnancy is associated with childhood wheeze, asthma and allergic rhinitis. Methods: We pooled individual data from 60 774 mother-child pairs participating in 18 European and US birth cohort studies. Information on wheeze, asthma and allergic rhinitis prevalence was collected using validated questionnaires. The time periods of interest were: infancy (0-2 ye…
Understanding the complexity of IgE-related phenotypes from childhood to young adulthood: A Mechanisms of the Development of Allergy (MeDALL) seminar.
Mechanisms of the Development of Allergy (MeDALL), a Seventh Framework Program European Union project, aims to generate novel knowledge on the mechanisms of initiation of allergy. Precise phenotypes of IgE-mediated allergic diseases will be defined in MeDALL. As part of MeDALL, a scientific seminar was held on January 24, 2011, to review current knowledge on the IgE-related phenotypes and to explore how a multidisciplinary effort could result in a new integrative translational approach. This article provides a summary of the meeting. It develops challenges in IgE-related phenotypes and new clinical and epidemiologic approaches to the investigation of allergic phenotypes, including cluster a…
Prenatal exposure to PCB-153, p,p'-DDE and birth outcomes in 9000 mother-child pairs: exposure-response relationship and effect modifiers.
Low-level exposure to polychlorinated biphenyl-153 (PCB-153) and dichlorodiphenyldichloroethylene (p-p′-DDE) can impair fetal growth; however, the exposure–response relationship and effect modifiers of such association are not well established. This study is an extension of an earlier European meta-analysis. Our aim was to explore exposure–response relationship between PCB-153 and p-p′-DDE and birth outcomes; to evaluate whether any no exposure–effect level and susceptible subgroups exist; and to assess the role of maternal gestational weight gain (GWG). We used a pooled dataset of 9377 mother–child pairs enrolled in 14 study populations from 11 European birth cohorts. General additive mode…
P046 Occupational exposures and gastric cancer risk in the MCC-spain case-control study
Objective To explore the relationship between gastric cancer (GC) and occupational exposures. Methods A total of 382 incident GC cases and 2,846 randomly selected population controls with occupational information were included from the MCC-Spain study, a population-based multicase-control study. Occupation was coded according to the Spanish National Classification of Occupations 1994. Occupational exposures were assessed by the MatEmEsp Job Exposure Matrix. ORs and their 95% confidence intervals (CI) were estimated by unconditional logistic regression adjusting for matching variables and education. Results In men, a statistically significant increased risk of GC, was found for ‘Employed ski…
Occurrence of DBPs in Drinking Water of European Regions for Epidemiology Studies
International audience; A three-year study was conducted on the occurrence of disinfection by-products (DBPs) - trihalomethanes (THMs), haloacetic acids (HAAs), and haloacetonitriles - in drinking water of regions of Europe where epidemiology studies were being carried out. Thirteen systems in six countries (i.e., Italy, France, Greece, Lithuania, Spain, United Kingdom) were sampled. Typically chlorinated DBPs dominated. However, in most of Catalonia (Spain) and in Heraklion (Greece), brominated DBPs dominated. The degree of bromine incorporation into the DBP classes was in general similar among them. This is important, as brominated DBPs are a greater health concern. In parts of Catalonia,…
DNA Methylation in Inflammatory Pathways Modifies the Association between BMI and Adult-Onset Non-Atopic Asthma
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 sit…
Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types
BACKGROUND: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites.METHODS: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cance…
Paving the way of systems biology and precision medicine in allergic diseases: the Me DALL success story
MeDALL (Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sen…
European code against cancer 4th edition: 12 ways to reduce your cancer risk
AbstractThis overview describes the principles of the 4th edition of the European Code against Cancer and provides an introduction to the 12 recommendations to reduce cancer risk. Among the 504.6 million inhabitants of the member states of the European Union (EU28), there are annually 2.64 million new cancer cases and 1.28 million deaths from cancer. It is estimated that this cancer burden could be reduced by up to one half if scientific knowledge on causes of cancer could be translated into successful prevention. The Code is a preventive tool aimed to reduce the cancer burden by informing people how to avoid or reduce carcinogenic exposures, adopt behaviours to reduce the cancer risk, or t…
Fish Intake in Pregnancy and Child Growth: A Pooled Analysis of 15 European and US Birth Cohorts
Importance Maternal fish intake in pregnancy has been shown to influence fetal growth. The extent to which fish intake affects childhood growth and obesity remains unclear. Objective To examine whether fish intake in pregnancy is associated with offspring growth and the risk of childhood overweight and obesity. Design, Setting, and Participants Multicenter, population-based birth cohort study of singleton deliveries from 1996 to 2011 in Belgium, France, Greece, Ireland, Italy, the Netherlands, Norway, Poland, Portugal, Spain, and Massachusetts. A total of 26 184 pregnant women and their children were followed up at 2-year intervals until the age of 6 years. Exposures Consumption of fish dur…
Maternal and fetal genetic contribution to gestational weight gain
Background: Clinical recommendations to limit gestational weight gain (GWG) imply high GWG is causally related to adverse outcomes in mother or offspring, but GWG is the sum of several inter-related complex phenotypes (maternal fat deposition and vascular expansion, placenta, amniotic fluid and fetal growth). Understanding the genetic contribution to GWG could help clarify the potential effect of its different components on maternal and offspring health. Here we explore the genetic contribution to total, early and late GWG. Participants and methods: A genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10 543 mothers and 16 317 offspri…
Association ofStreptococcus gallolyticussubspeciesgallolyticuswith colorectal cancer: Serological evidence
The colonic opportunist Streptococcus gallolyticus subspecies gallolyticus (SGG) is potentially associated with colorectal cancer (CRC). Large-scale seroepidemiological data for SGG antibodies and their possible association with CRC is currently missing. Associations between CRC and antibody responses to SGG were examined in 576 CRC cases and 576 controls matched by sex, age and province from a population-based multicase-control project (MCC-Spain). MCC-Spain was conducted between 2008 and 2013 in 12 Spanish provinces. Antibody responses to recombinant affinity-purified SGG pilus proteins Gallo1569, 2039, 2178 and 2179 were analysed by multiplex serology. Polyomavirus (PyV) JC VP1 and PyV 6…
Shared DNA methylation signatures in childhood allergy: The MeDALL study
Contains fulltext : 232514.pdf (Publisher’s version ) (Open Access) BACKGROUND: Differential DNA methylation associated with allergy might provide novel insights into the shared or unique etiology of asthma, rhinitis, and eczema. OBJECTIVE: We sought to identify DNA methylation profiles associated with childhood allergy. METHODS: Within the European Mechanisms of the Development of Allergy (MeDALL) consortium, we performed an epigenome-wide association study of whole blood DNA methylation by using a cross-sectional design. Allergy was defined as having symptoms from at least 1 allergic disease (asthma, rhinitis, or eczema) and positive serum-specific IgE to common aeroallergens. The discove…
Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder
Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generat…
Postnatal weight growth and trihalomethane exposure during pregnancy.
Abstract Background Impaired postnatal growth after chloroform exposure in utero has been observed in rodents without an effect on birth weight. We aimed to study the relationship between exposure to trihalomethanes (THMs) during pregnancy and postnatal weight growth during infancy. Methods We analysed 2216 mother–child pairs recruited in Gipuzkoa, Sabadell, Valencia (Spain, INMA Project, enrolment: 2003–2008) and Crete (Greece, RHEA Study, enrolment: 2007–2008). Drinking water habits and water-related activities ascertained through personal interviews were combined with THM measurements in drinking water to estimate THM exposure through different exposure routes during pregnancy. Weight me…
The independent role of prenatal and postnatal exposure to active and passive smoking on the development of early wheeze in children
Maternal smoking during pregnancy increases childhood asthma risk, but health effects in children of nonsmoking mothers passively exposed to tobacco smoke during pregnancy are unclear. We examined the association of maternal passive smoking during pregnancy and wheeze in children aged ≤2 years.Individual data of 27 993 mother–child pairs from 15 European birth cohorts were combined in pooled analyses taking into consideration potential confounders.Children with maternal exposure to passive smoking during pregnancy and no other smoking exposure were more likely to develop wheeze up to the age of 2 years (OR 1.11, 95% CI 1.03–1.20) compared with unexposed children. Risk of wheeze was further …