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Prof. Dr. Soterios Kyrtopoulos
National Hellenic Research Foundation, Institute of Chemical Biology, Vas. Constantinou 48, 11635 Athens, Greece

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0 Biomarkers
0 Cancer Epidemiology
0 Environmental Toxicology
0 Environmental genomics
0 DNA Damage and Repair

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Cancer Epidemiology

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Journal article
Published: 01 August 2020 in Epigenomics
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Aim: Inflammation represents a potential pathway through which socioeconomic position (SEP) is biologically embedded. Materials & methods: We analyzed inflammatory biomarkers in response to life course SEP by integrating multi-omics DNA-methylation, gene expression and protein level in 178 European Prospective Investigation into Cancer and Nutrition-Italy participants. Results & conclusion: We identified 61 potential cis acting CpG loci whose methylation levels were associated with gene expression at a Bonferroni correction. We examined the relationships between life course SEP and these 61 cis-acting regulatory methylation sites individually and jointly using several scores. Less-advantaged SEP participants exhibit, later in life, a lower inflammatory methylome score, suggesting an overall increased expression of the corresponding inflammatory genes or proteins, supporting the hypothesis that SEP impacts adult physiology through inflammation.

ACS Style

Raphaële Castagné; Michelle Kelly-Irving; Vittorio Krogh; Domenico Palli; Salvatore Panico; Carlotta Sacerdote; Rosario Tumino; Dennie Gaj Hebels; Jos Cs Kleinjans; Theo Mcm De Kok; Panagiotis Georgiadis; Soterios A Kyrtopoulos; Roel Vermeulen; Silvia Stringhini; Paolo Vineis; Marc Chadeau-Hyam‡; Cyrille Delpierre‡. A multi-omics approach to investigate the inflammatory response to life course socioeconomic position. Epigenomics 2020, 12, 1 .

AMA Style

Raphaële Castagné, Michelle Kelly-Irving, Vittorio Krogh, Domenico Palli, Salvatore Panico, Carlotta Sacerdote, Rosario Tumino, Dennie Gaj Hebels, Jos Cs Kleinjans, Theo Mcm De Kok, Panagiotis Georgiadis, Soterios A Kyrtopoulos, Roel Vermeulen, Silvia Stringhini, Paolo Vineis, Marc Chadeau-Hyam‡, Cyrille Delpierre‡. A multi-omics approach to investigate the inflammatory response to life course socioeconomic position. Epigenomics. 2020; 12 (15):1.

Chicago/Turabian Style

Raphaële Castagné; Michelle Kelly-Irving; Vittorio Krogh; Domenico Palli; Salvatore Panico; Carlotta Sacerdote; Rosario Tumino; Dennie Gaj Hebels; Jos Cs Kleinjans; Theo Mcm De Kok; Panagiotis Georgiadis; Soterios A Kyrtopoulos; Roel Vermeulen; Silvia Stringhini; Paolo Vineis; Marc Chadeau-Hyam‡; Cyrille Delpierre‡. 2020. "A multi-omics approach to investigate the inflammatory response to life course socioeconomic position." Epigenomics 12, no. 15: 1.

Review article
Published: 11 March 2019 in Archives of Toxicology
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The factors underlying the increasing rates and the geographic variation of childhood cancers are largely unknown. Epidemiological studies provide limited evidence for a possible role in the etiology of certain types of childhood cancer of the exposure of pregnant women to environmental carcinogens (e.g., tobacco smoke and pesticides); however, such evidence is inadequate to allow definitive conclusions. Complementary evidence can be obtained from biomarker-based population studies. Such studies have demonstrated that, following exposure of pregnant mothers, most environmental carcinogens reach the fetus and, in many cases, induce therein genotoxic damage which in adults is known to be associated with increased cancer risk, implying that environmental carcinogens may contribute to the etiology of childhood cancer. During recent years, intermediate disease biomarkers, obtained via omic profiling, have provided additional insights into the impact of transplacental exposures on fetal tissues which, in some cases, are also compatible with a precarcinogenic role of certain in utero exposures. Here we review the epidemiological and biomarker evidence and discuss how further research, especially utilizing high-density profiling, may allow a better evaluation of the links between in utero environmental exposures and cancer in children.

ACS Style

Maria Botsivali; Soterios A. Kyrtopoulos. Transplacental exposure to carcinogens and risks to children: evidence from biomarker studies and the utility of omic profiling. Archives of Toxicology 2019, 93, 1 -25.

AMA Style

Maria Botsivali, Soterios A. Kyrtopoulos. Transplacental exposure to carcinogens and risks to children: evidence from biomarker studies and the utility of omic profiling. Archives of Toxicology. 2019; 93 (4):1-25.

Chicago/Turabian Style

Maria Botsivali; Soterios A. Kyrtopoulos. 2019. "Transplacental exposure to carcinogens and risks to children: evidence from biomarker studies and the utility of omic profiling." Archives of Toxicology 93, no. 4: 1-25.

Journal article
Published: 15 February 2019 in Environment International
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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. 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. 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. 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 of the potential toxicity of environmental chemicals.

ACS Style

Panagiotis Georgiadis; Marios Gavriil; Panu Rantakokko; Efthymios Ladoukakis; Maria Botsivali; Rachel S. Kelly; Ingvar A. Bergdahl; Hannu Kiviranta; Roel C.H. Vermeulen; Florentin Spaeth; Dennie G.A.J. Hebbels; Jos C.S. Kleinjans; Theo M.C.M. de Kok; Domenico Palli; Paolo Vineis; Soterios A. Kyrtopoulos. DNA methylation profiling implicates exposure to PCBs in the pathogenesis of B-cell chronic lymphocytic leukemia. Environment International 2019, 126, 24 -36.

AMA Style

Panagiotis Georgiadis, Marios Gavriil, Panu Rantakokko, Efthymios Ladoukakis, Maria Botsivali, Rachel S. Kelly, Ingvar A. Bergdahl, Hannu Kiviranta, Roel C.H. Vermeulen, Florentin Spaeth, Dennie G.A.J. Hebbels, Jos C.S. Kleinjans, Theo M.C.M. de Kok, Domenico Palli, Paolo Vineis, Soterios A. Kyrtopoulos. DNA methylation profiling implicates exposure to PCBs in the pathogenesis of B-cell chronic lymphocytic leukemia. Environment International. 2019; 126 ():24-36.

Chicago/Turabian Style

Panagiotis Georgiadis; Marios Gavriil; Panu Rantakokko; Efthymios Ladoukakis; Maria Botsivali; Rachel S. Kelly; Ingvar A. Bergdahl; Hannu Kiviranta; Roel C.H. Vermeulen; Florentin Spaeth; Dennie G.A.J. Hebbels; Jos C.S. Kleinjans; Theo M.C.M. de Kok; Domenico Palli; Paolo Vineis; Soterios A. Kyrtopoulos. 2019. "DNA methylation profiling implicates exposure to PCBs in the pathogenesis of B-cell chronic lymphocytic leukemia." Environment International 126, no. : 24-36.

Journal article
Published: 01 February 2019 in International Journal of Environmental Research and Public Health
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Background: Lead exposure, even at low levels, is associated with adverse health effects in humans. We investigated the determinants of individual lead levels in a general population-based sample of adults from Florence, Italy. Methods: Erythrocyte lead levels were measured (using inductively coupled plasma-mass spectrometry) in 454 subjects enrolled in the Florence cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC) study in 1992–1998. Multiple linear regression models were used to study the association between demographics, education and working history, lifestyle, dietary habits, anthropometry, residential history, and (among women) menstrual and reproductive history and use of exogenous sex hormones, and erythrocyte lead levels. Results: Median lead levels were 86.1 μg/L (inter-quartile range 65.5–111.9 μg/L). Male gender, older age, cigarette smoking and number of pack-years, alcohol intake, and residing in urban areas were positively associated with higher erythrocyte lead levels, while performing professional/managerial or administrative work or being retired was inversely associated with lead levels. Among women, lead levels were higher for those already in menopause, and lower among those who ever used hormone replacement therapy. Conclusions: Avoidable risk factors contribute to the lead body burden among adults, which could therefore be lowered through targeted public health measures.

ACS Style

Saverio Caini; Benedetta Bendinelli; Giovanna Masala; Calogero Saieva; Melania Assedi; Andrea Querci; Thomas Lundh; Soterios A. Kyrtopoulos; Domenico Palli. Determinants of Erythrocyte Lead Levels in 454 Adults in Florence, Italy. International Journal of Environmental Research and Public Health 2019, 16, 425 .

AMA Style

Saverio Caini, Benedetta Bendinelli, Giovanna Masala, Calogero Saieva, Melania Assedi, Andrea Querci, Thomas Lundh, Soterios A. Kyrtopoulos, Domenico Palli. Determinants of Erythrocyte Lead Levels in 454 Adults in Florence, Italy. International Journal of Environmental Research and Public Health. 2019; 16 (3):425.

Chicago/Turabian Style

Saverio Caini; Benedetta Bendinelli; Giovanna Masala; Calogero Saieva; Melania Assedi; Andrea Querci; Thomas Lundh; Soterios A. Kyrtopoulos; Domenico Palli. 2019. "Determinants of Erythrocyte Lead Levels in 454 Adults in Florence, Italy." International Journal of Environmental Research and Public Health 16, no. 3: 425.

Journal article
Published: 24 January 2019 in Scientific Reports
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PCBs are classified as xenoestrogens and carcinogens and their health risks may be sex-specific. To identify potential sex-specific responses to PCB-exposure we established gene expression profiles in a population study subdivided into females and males. Gene expression profiles were determined in a study population consisting of 512 subjects from the EnviroGenomarkers project, 217 subjects who developed lymphoma and 295 controls were selected in later life. We ran linear mixed models in order to find associations between gene expression and exposure to PCBs, while correcting for confounders, in particular distribution of white blood cells (WBC), as well as random effects. The analysis was subdivided according to sex and development of lymphoma in later life. The changes in gene expression as a result of exposure to the six studied PCB congeners were sex- and WBC type specific. The relatively large number of genes that are significantly associated with PCB-exposure in the female subpopulation already indicates different biological response mechanisms to PCBs between the two sexes. The interaction analysis between different PCBs and WBCs provides only a small overlap between sexes. In males, cancer-related pathways and in females immune system-related pathways are identified in association with PCBs and WBCs. Future lymphoma cases and controls for both sexes show different responses to the interaction of PCBs with WBCs, suggesting a role of the immune system in PCB-related cancer development.

ACS Style

Almudena Espín-Pérez; Dennie Hebels; Hannu Kiviranta; Panu Rantakokko; Panagiotis Georgiadis; Maria Botsivali; Ingvar A. Bergdahl; Domenico Palli; Florentin Späth; Anders Johansson; Marc Chadeau-Hyam; Soterios A. Kyrtopoulos; Jos C. S. Kleinjans; Theo M. C. M. De Kok. Identification of Sex-Specific Transcriptome Responses to Polychlorinated Biphenyls (PCBs). Scientific Reports 2019, 9, 1 -12.

AMA Style

Almudena Espín-Pérez, Dennie Hebels, Hannu Kiviranta, Panu Rantakokko, Panagiotis Georgiadis, Maria Botsivali, Ingvar A. Bergdahl, Domenico Palli, Florentin Späth, Anders Johansson, Marc Chadeau-Hyam, Soterios A. Kyrtopoulos, Jos C. S. Kleinjans, Theo M. C. M. De Kok. Identification of Sex-Specific Transcriptome Responses to Polychlorinated Biphenyls (PCBs). Scientific Reports. 2019; 9 (1):1-12.

Chicago/Turabian Style

Almudena Espín-Pérez; Dennie Hebels; Hannu Kiviranta; Panu Rantakokko; Panagiotis Georgiadis; Maria Botsivali; Ingvar A. Bergdahl; Domenico Palli; Florentin Späth; Anders Johansson; Marc Chadeau-Hyam; Soterios A. Kyrtopoulos; Jos C. S. Kleinjans; Theo M. C. M. De Kok. 2019. "Identification of Sex-Specific Transcriptome Responses to Polychlorinated Biphenyls (PCBs)." Scientific Reports 9, no. 1: 1-12.

Cancer epidemiology
Published: 17 August 2018 in International Journal of Cancer
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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.

ACS Style

Mia M. Gaudet; Emily L. Deubler; Rachel S. Kelly; W. Ryan Diver; Lauren R. Teras; James M. Hodge; Keith Levine; Laura G. Haines; Thomas Lundh; Per Lenner; Domenico Palli; Paolo Vineis; Ingvar A. Bergdahl; Susan M. Gapstur; Soterios A. Kyrtopoulos. Blood levels of cadmium and lead in relation to breast cancer risk in three prospective cohorts. International Journal of Cancer 2018, 144, 1010 -1016.

AMA Style

Mia M. Gaudet, Emily L. Deubler, Rachel S. Kelly, W. Ryan Diver, Lauren R. Teras, James M. Hodge, Keith Levine, Laura G. Haines, Thomas Lundh, Per Lenner, Domenico Palli, Paolo Vineis, Ingvar A. Bergdahl, Susan M. Gapstur, Soterios A. Kyrtopoulos. Blood levels of cadmium and lead in relation to breast cancer risk in three prospective cohorts. International Journal of Cancer. 2018; 144 (5):1010-1016.

Chicago/Turabian Style

Mia M. Gaudet; Emily L. Deubler; Rachel S. Kelly; W. Ryan Diver; Lauren R. Teras; James M. Hodge; Keith Levine; Laura G. Haines; Thomas Lundh; Per Lenner; Domenico Palli; Paolo Vineis; Ingvar A. Bergdahl; Susan M. Gapstur; Soterios A. Kyrtopoulos. 2018. "Blood levels of cadmium and lead in relation to breast cancer risk in three prospective cohorts." International Journal of Cancer 144, no. 5: 1010-1016.

Journal article
Published: 17 July 2018 in Scientific Reports
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Chronic inflammation may be involved in cancer development and progression. Using 28 inflammatory-related proteins collected from prospective blood samples from two case-control studies nested in the Italian component of the European Prospective Investigation into Cancer and nutrition (n = 261) and in the Northern Sweden Health and Disease Study (n = 402), we tested the hypothesis that an inflammatory score is associated with breast cancer (BC) and Β-cell Non-Hodgkin Lymphoma (B-cell NHL, including 68 multiple myeloma cases) onset. We modelled the relationship between this inflammatory score and the two cancers studied: (BC and B-cell NHL) using generalised linear models, and assessed, through adjustments the role of behaviours and lifestyle factors. Analyses were performed by cancer types pooling both populations, and stratified by cohorts, and time to diagnosis. Our results suggested a lower inflammatory score in B-cell NHL cases (β = −1.28, p = 0.012), and, to lesser, extent with BC (β = −0.96, p = 0.33) compared to controls, mainly driven by cancer cases diagnosed less than 6 years after enrolment. These associations were not affected by subsequent adjustments for potential intermediate confounders, notably behaviours. Sensitivity analyses indicated that our findings were not affected by the way the inflammatory score was calculated. These observations call for further studies involving larger populations, larger variety of cancer types and repeated measures of larger panel of inflammatory markers.

ACS Style

Eloise Berger; Enviro Geno Markers; Cyrille Delpierre; Fatemeh Saberi Hosnijeh; Michelle Kelly-Irving; Lutzen Portengen; Ingvar A. Bergdahl; Ann-Sofie Johansson; Vittorio Krogh; Domenico Palli; Salvatore Panico; Carlotta Sacerdote; Rosario Tumino; Soterios A. Kyrtopoulos; Paolo Vineis; Marc Chadeau-Hyam; Roel Vermeulen; Raphaële Castagné. Association between low-grade inflammation and Breast cancer and B-cell Myeloma and Non-Hodgkin Lymphoma: findings from two prospective cohorts. Scientific Reports 2018, 8, 10805 .

AMA Style

Eloise Berger, Enviro Geno Markers, Cyrille Delpierre, Fatemeh Saberi Hosnijeh, Michelle Kelly-Irving, Lutzen Portengen, Ingvar A. Bergdahl, Ann-Sofie Johansson, Vittorio Krogh, Domenico Palli, Salvatore Panico, Carlotta Sacerdote, Rosario Tumino, Soterios A. Kyrtopoulos, Paolo Vineis, Marc Chadeau-Hyam, Roel Vermeulen, Raphaële Castagné. Association between low-grade inflammation and Breast cancer and B-cell Myeloma and Non-Hodgkin Lymphoma: findings from two prospective cohorts. Scientific Reports. 2018; 8 (1):10805.

Chicago/Turabian Style

Eloise Berger; Enviro Geno Markers; Cyrille Delpierre; Fatemeh Saberi Hosnijeh; Michelle Kelly-Irving; Lutzen Portengen; Ingvar A. Bergdahl; Ann-Sofie Johansson; Vittorio Krogh; Domenico Palli; Salvatore Panico; Carlotta Sacerdote; Rosario Tumino; Soterios A. Kyrtopoulos; Paolo Vineis; Marc Chadeau-Hyam; Roel Vermeulen; Raphaële Castagné. 2018. "Association between low-grade inflammation and Breast cancer and B-cell Myeloma and Non-Hodgkin Lymphoma: findings from two prospective cohorts." Scientific Reports 8, no. 1: 10805.

Journal article
Published: 01 May 2018 in International Journal of Obesity
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Obesity 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. DNA 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. We 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 associated with myocardial infarction (P < 1.25×10−3), independently of obesity and established risk factors. Our results suggest that epigenetic changes, in particular altered DNA methylation patterns, may be an intermediate biomarker at the intersection of obesity and obesity-related diseases, and could offer clues as to underlying biological mechanisms.

ACS Style

Gianluca Campanella; Marc J. Gunter; Silvia Polidoro; Vittorio Krogh; Domenico Palli; Salvatore Panico; Carlotta Sacerdote; Rosario Tumino; Giovanni Fiorito; Simonetta Guarrera; Licia Iacoviello; Ingvar A. Bergdahl; Beatrice Melin; Per Lenner; Theo M. C. M. De Kok; Panagiotis Georgiadis; Jos C. S. Kleinjans; Soterios A. Kyrtopoulos; H. Bas Bueno-De-Mesquita; Karen Lillycrop; Anne M. May; N. Charlotte Onland-Moret; Robert Murray; Elio Riboli; Monique Verschuren; Eiliv Lund; Nicolle Mode; Torkjel M. Sandanger; Valentina Fiano; Morena Trevisan; Giuseppe Matullo; Philippe Froguel; Paul Elliott; Paolo Vineis; Marc Chadeau-Hyam. Epigenome-wide association study of adiposity and future risk of obesity-related diseases. International Journal of Obesity 2018, 42, 2022 -2035.

AMA Style

Gianluca Campanella, Marc J. Gunter, Silvia Polidoro, Vittorio Krogh, Domenico Palli, Salvatore Panico, Carlotta Sacerdote, Rosario Tumino, Giovanni Fiorito, Simonetta Guarrera, Licia Iacoviello, Ingvar A. Bergdahl, Beatrice Melin, Per Lenner, Theo M. C. M. De Kok, Panagiotis Georgiadis, Jos C. S. Kleinjans, Soterios A. Kyrtopoulos, H. Bas Bueno-De-Mesquita, Karen Lillycrop, Anne M. May, N. Charlotte Onland-Moret, Robert Murray, Elio Riboli, Monique Verschuren, Eiliv Lund, Nicolle Mode, Torkjel M. Sandanger, Valentina Fiano, Morena Trevisan, Giuseppe Matullo, Philippe Froguel, Paul Elliott, Paolo Vineis, Marc Chadeau-Hyam. Epigenome-wide association study of adiposity and future risk of obesity-related diseases. International Journal of Obesity. 2018; 42 (12):2022-2035.

Chicago/Turabian Style

Gianluca Campanella; Marc J. Gunter; Silvia Polidoro; Vittorio Krogh; Domenico Palli; Salvatore Panico; Carlotta Sacerdote; Rosario Tumino; Giovanni Fiorito; Simonetta Guarrera; Licia Iacoviello; Ingvar A. Bergdahl; Beatrice Melin; Per Lenner; Theo M. C. M. De Kok; Panagiotis Georgiadis; Jos C. S. Kleinjans; Soterios A. Kyrtopoulos; H. Bas Bueno-De-Mesquita; Karen Lillycrop; Anne M. May; N. Charlotte Onland-Moret; Robert Murray; Elio Riboli; Monique Verschuren; Eiliv Lund; Nicolle Mode; Torkjel M. Sandanger; Valentina Fiano; Morena Trevisan; Giuseppe Matullo; Philippe Froguel; Paul Elliott; Paolo Vineis; Marc Chadeau-Hyam. 2018. "Epigenome-wide association study of adiposity and future risk of obesity-related diseases." International Journal of Obesity 42, no. 12: 2022-2035.

Correspondence
Published: 15 February 2018 in BMC Public Health
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The final meeting of the EXPOsOMICS project “Final Policy Workshop and Stakeholder Consultation” took place 28–29 March 2017 to present the main results of the project and discuss their implications both for future research and for regulatory and policy activities. This paper summarizes presentations and discussions at the meeting related with the main results and advances in exposome research achieved through the EXPOsOMICS project; on other parallel research initiatives on the study of the exposome in Europe and in the United States and their complementarity to EXPOsOMICS; lessons learned from these early studies on the exposome and how they may shape the future of research on environmental exposure assessment; and finally the broader implications of exposome research for risk assessment and policy development on environmental exposures. The main results of EXPOsOMICS in relation to studies of the external exposome and internal exposome in relation to both air pollution and water contaminants were presented as well as new technologies for environmental health research (adductomics) and advances in statistical methods. Although exposome research strengthens the scientific basis for policy development, there is a need in terms of showing added value for public health to: improve communication of research results to non-scientific audiences; target research to the broader landscape of societal challenges; and draw applicable conclusions. Priorities for future work include the development and standardization of methodologies and technologies for assessing the external and internal exposome, improved data sharing and integration, and the demonstration of the added value of exposome science over conventional approaches in answering priority policy questions.

ACS Style

Michelle C. Turner; on behalf of the EXPOsOMICS Consortium; Paolo Vineis; Eduardo Seleiro; Michaela Dijmarescu; David Balshaw; Roberto Bertollini; Marc Chadeau-Hyam; Timothy Gant; John Gulliver; Ayoung Jeong; Soterios Kyrtopoulos; Marco Martuzzi; Gary W. Miller; Timothy Nawrot; Mark Nieuwenhuijsen; David H. Phillips; Nicole Probst-Hensch; Jonathan Samet; Roel Vermeulen; Jelle Vlaanderen; Martine Vrijheid; Christopher Wild; Manolis Kogevinas. EXPOsOMICS: final policy workshop and stakeholder consultation. BMC Public Health 2018, 18, 1 -11.

AMA Style

Michelle C. Turner, on behalf of the EXPOsOMICS Consortium, Paolo Vineis, Eduardo Seleiro, Michaela Dijmarescu, David Balshaw, Roberto Bertollini, Marc Chadeau-Hyam, Timothy Gant, John Gulliver, Ayoung Jeong, Soterios Kyrtopoulos, Marco Martuzzi, Gary W. Miller, Timothy Nawrot, Mark Nieuwenhuijsen, David H. Phillips, Nicole Probst-Hensch, Jonathan Samet, Roel Vermeulen, Jelle Vlaanderen, Martine Vrijheid, Christopher Wild, Manolis Kogevinas. EXPOsOMICS: final policy workshop and stakeholder consultation. BMC Public Health. 2018; 18 (1):1-11.

Chicago/Turabian Style

Michelle C. Turner; on behalf of the EXPOsOMICS Consortium; Paolo Vineis; Eduardo Seleiro; Michaela Dijmarescu; David Balshaw; Roberto Bertollini; Marc Chadeau-Hyam; Timothy Gant; John Gulliver; Ayoung Jeong; Soterios Kyrtopoulos; Marco Martuzzi; Gary W. Miller; Timothy Nawrot; Mark Nieuwenhuijsen; David H. Phillips; Nicole Probst-Hensch; Jonathan Samet; Roel Vermeulen; Jelle Vlaanderen; Martine Vrijheid; Christopher Wild; Manolis Kogevinas. 2018. "EXPOsOMICS: final policy workshop and stakeholder consultation." BMC Public Health 18, no. 1: 1-11.

Journal article
Published: 24 November 2017 in Scientific Reports
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Low socioeconomic status (SES) is associated with earlier onset of age-related chronic conditions and reduced life-expectancy, but the underlying biomolecular mechanisms remain unclear. Evidence of DNA-methylation differences by SES suggests a possible association of SES with epigenetic age acceleration (AA). We investigated the association of SES with AA in more than 5,000 individuals belonging to three independent prospective cohorts from Italy, Australia, and Ireland. Low SES was associated with greater AA (β = 0.99 years; 95% CI 0.39,1.59; p = 0.002; comparing extreme categories). The results were consistent across different SES indicators. The associations were only partially modulated by the unhealthy lifestyle habits of individuals with lower SES. Individuals who experienced life-course SES improvement had intermediate AA compared to extreme SES categories, suggesting reversibility of the effect and supporting the relative importance of the early childhood social environment. Socioeconomic adversity is associated with accelerated epigenetic aging, implicating biomolecular mechanisms that may link SES to age-related diseases and longevity.

ACS Style

Giovanni Fiorito; Silvia Polidoro; Pierre-Antoine Dugue; Mika Kivimaki; Erica Ponzi; Giuseppe Matullo; Simonetta Guarrera; Manuela B. Assumma; Panagiotis Georgiadis; Soterios A. Kyrtopoulos; Vittorio Krogh; Domenico Palli; Salvatore Panico; Carlotta Sacerdote; Rosario Tumino; Marc Chadeau-Hyam; Silvia Stringhini; Gianluca Severi; Allison Hodge; Graham G. Giles; Riccardo Marioni; Richard Karlsson Linnér; Aisling O'Halloran; Rose Anne Kenny; Richard Layte; Laura Baglietto; Oliver Robinson; Cathal McCrory; Roger L. Milne; Paolo Vineis. Social adversity and epigenetic aging: a multi-cohort study on socioeconomic differences in peripheral blood DNA methylation. Scientific Reports 2017, 7, 1 -12.

AMA Style

Giovanni Fiorito, Silvia Polidoro, Pierre-Antoine Dugue, Mika Kivimaki, Erica Ponzi, Giuseppe Matullo, Simonetta Guarrera, Manuela B. Assumma, Panagiotis Georgiadis, Soterios A. Kyrtopoulos, Vittorio Krogh, Domenico Palli, Salvatore Panico, Carlotta Sacerdote, Rosario Tumino, Marc Chadeau-Hyam, Silvia Stringhini, Gianluca Severi, Allison Hodge, Graham G. Giles, Riccardo Marioni, Richard Karlsson Linnér, Aisling O'Halloran, Rose Anne Kenny, Richard Layte, Laura Baglietto, Oliver Robinson, Cathal McCrory, Roger L. Milne, Paolo Vineis. Social adversity and epigenetic aging: a multi-cohort study on socioeconomic differences in peripheral blood DNA methylation. Scientific Reports. 2017; 7 (1):1-12.

Chicago/Turabian Style

Giovanni Fiorito; Silvia Polidoro; Pierre-Antoine Dugue; Mika Kivimaki; Erica Ponzi; Giuseppe Matullo; Simonetta Guarrera; Manuela B. Assumma; Panagiotis Georgiadis; Soterios A. Kyrtopoulos; Vittorio Krogh; Domenico Palli; Salvatore Panico; Carlotta Sacerdote; Rosario Tumino; Marc Chadeau-Hyam; Silvia Stringhini; Gianluca Severi; Allison Hodge; Graham G. Giles; Riccardo Marioni; Richard Karlsson Linnér; Aisling O'Halloran; Rose Anne Kenny; Richard Layte; Laura Baglietto; Oliver Robinson; Cathal McCrory; Roger L. Milne; Paolo Vineis. 2017. "Social adversity and epigenetic aging: a multi-cohort study on socioeconomic differences in peripheral blood DNA methylation." Scientific Reports 7, no. 1: 1-12.

Research article
Published: 13 September 2017 in BMC Genomics
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B-cell chronic lymphocytic leukemia (CLL) is a common type of adult leukemia. It often follows an indolent course and is preceded by monoclonal B-cell lymphocytosis, an asymptomatic condition, however it is not known what causes subjects with this condition to progress to CLL. Hence the discovery of prediagnostic markers has the potential to improve the identification of subjects likely to develop CLL and may also provide insights into the pathogenesis of the disease of potential clinical relevance. We employed peripheral blood buffy coats of 347 apparently healthy subjects, of whom 28 were diagnosed with CLL 2.0–15.7 years after enrollment, to derive for the first time genome-wide DNA methylation, as well as gene and miRNA expression, profiles associated with the risk of future disease. After adjustment for white blood cell composition, we identified 722 differentially methylated CpG sites and 15 differentially expressed genes (Bonferroni-corrected p < 0.05) as well as 2 miRNAs (FDR < 0.05) which were associated with the risk of future CLL. The majority of these signals have also been observed in clinical CLL, suggesting the presence in prediagnostic blood of CLL-like cells. Future CLL cases who, at enrollment, had a relatively low B-cell fraction (<10%), and were therefore less likely to have been suffering from undiagnosed CLL or a precursor condition, showed profiles involving smaller numbers of the same differential signals with intensities, after adjusting for B-cell content, generally smaller than those observed in the full set of cases. A similar picture was obtained when the differential profiles of cases with time-to-diagnosis above the overall median period of 7.4 years were compared with those with shorted time-to-disease. Differentially methylated genes of major functional significance include numerous genes that encode for transcription factors, especially members of the homeobox family, while differentially expressed genes include, among others, multiple genes related to WNT signaling as well as the miRNAs miR-150-5p and miR-155-5p. Our findings demonstrate the presence in prediagnostic blood of future CLL patients, more than 10 years before diagnosis, of CLL-like cells which evolve as preclinical disease progresses, and point to early molecular alterations with a pathogenetic potential.

ACS Style

Panagiotis Georgiadis; on behalf of the EnviroGenomarkers consortium; Irene Liampa; Dennie G. Hebels; Julian Krauskopf; Aristotelis Chatziioannou; Ioannis Valavanis; Theo M.C.M. de Kok; Jos C.S. Kleinjans; Ingvar A. Bergdahl; Beatrice Melin; Florentin Spaeth; Domenico Palli; R.C.H. Vermeulen; J. Vlaanderen; Marc Chadeau-Hyam; Paolo Vineis; Soterios A. Kyrtopoulos. Evolving DNA methylation and gene expression markers of B-cell chronic lymphocytic leukemia are present in pre-diagnostic blood samples more than 10 years prior to diagnosis. BMC Genomics 2017, 18, 728 .

AMA Style

Panagiotis Georgiadis, on behalf of the EnviroGenomarkers consortium, Irene Liampa, Dennie G. Hebels, Julian Krauskopf, Aristotelis Chatziioannou, Ioannis Valavanis, Theo M.C.M. de Kok, Jos C.S. Kleinjans, Ingvar A. Bergdahl, Beatrice Melin, Florentin Spaeth, Domenico Palli, R.C.H. Vermeulen, J. Vlaanderen, Marc Chadeau-Hyam, Paolo Vineis, Soterios A. Kyrtopoulos. Evolving DNA methylation and gene expression markers of B-cell chronic lymphocytic leukemia are present in pre-diagnostic blood samples more than 10 years prior to diagnosis. BMC Genomics. 2017; 18 (1):728.

Chicago/Turabian Style

Panagiotis Georgiadis; on behalf of the EnviroGenomarkers consortium; Irene Liampa; Dennie G. Hebels; Julian Krauskopf; Aristotelis Chatziioannou; Ioannis Valavanis; Theo M.C.M. de Kok; Jos C.S. Kleinjans; Ingvar A. Bergdahl; Beatrice Melin; Florentin Spaeth; Domenico Palli; R.C.H. Vermeulen; J. Vlaanderen; Marc Chadeau-Hyam; Paolo Vineis; Soterios A. Kyrtopoulos. 2017. "Evolving DNA methylation and gene expression markers of B-cell chronic lymphocytic leukemia are present in pre-diagnostic blood samples more than 10 years prior to diagnosis." BMC Genomics 18, no. 1: 728.

Journal article
Published: 24 August 2017 in Environment International
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Long-term exposure to air pollution has been associated with several adverse health effects including cardiovascular, respiratory diseases and cancers. However, underlying molecular alterations remain to be further investigated. The aim of this study is to investigate the effects of long-term exposure to air pollutants on (a) average DNA methylation at functional regions and, (b) individual differentially methylated CpG sites. An assumption is that omic measurements, including the methylome, are more sensitive to low doses than hard health outcomes. This study included blood-derived DNA methylation (Illumina-HM450 methylation) for 454 Italian and 159 Dutch participants from the European Prospective Investigation into Cancer and Nutrition (EPIC). Long-term air pollution exposure levels, including NO2, NOx, PM2.5, PMcoarse, PM10, PM2.5 absorbance (soot) were estimated using models developed within the ESCAPE project, and back-extrapolated to the time of sampling when possible. We meta-analysed the associations between the air pollutants and global DNA methylation, methylation in functional regions and epigenome-wide methylation. CpG sites found differentially methylated with air pollution were further investigated for functional interpretation in an independent population (EnviroGenoMarkers project), where (N = 613) participants had both methylation and gene expression data available. Exposure to NO2 was associated with a significant global somatic hypomethylation (p-value = 0.014). Hypomethylation of CpG island's shores and shelves and gene bodies was significantly associated with higher exposures to NO2 and NOx. Meta-analysing the epigenome-wide findings of the 2 cohorts did not show genome-wide significant associations at single CpG site level. However, several significant CpG were found if the analyses were separated by countries. By regressing gene expression levels against methylation levels of the exposure-related CpG sites, we identified several significant CpG-transcript pairs and highlighted 5 enriched pathways for NO2 and 9 for NOx mainly related to the immune system and its regulation. Our findings support results on global hypomethylation associated with air pollution, and suggest that the shores and shelves of CpG islands and gene bodies are mostly affected by higher exposure to NO2 and NOx. Functional differences in the immune system were suggested by transcriptome analyses.

ACS Style

Michelle Plusquin; Florence Guida; Silvia Polidoro; Roel Vermeulen; Ole Raaschou-Nielsen; Gianluca Campanella; Gerard Hoek; Soterios Kyrtopoulos; Panagiotis Georgiadis; Alessio Naccarati; Carlotta Sacerdote; Vittorio Krogh; H. Bas Bueno-De-Mesquita; W.M. Monique Verschuren; Sergi Sayols Baixeras; Tommaso Panni; Annette Peters; Dennie Hebels; Jos Kleinjans; Paolo Vineis; Marc Chadeau-Hyam. DNA methylation and exposure to ambient air pollution in two prospective cohorts. Environment International 2017, 108, 127 -136.

AMA Style

Michelle Plusquin, Florence Guida, Silvia Polidoro, Roel Vermeulen, Ole Raaschou-Nielsen, Gianluca Campanella, Gerard Hoek, Soterios Kyrtopoulos, Panagiotis Georgiadis, Alessio Naccarati, Carlotta Sacerdote, Vittorio Krogh, H. Bas Bueno-De-Mesquita, W.M. Monique Verschuren, Sergi Sayols Baixeras, Tommaso Panni, Annette Peters, Dennie Hebels, Jos Kleinjans, Paolo Vineis, Marc Chadeau-Hyam. DNA methylation and exposure to ambient air pollution in two prospective cohorts. Environment International. 2017; 108 ():127-136.

Chicago/Turabian Style

Michelle Plusquin; Florence Guida; Silvia Polidoro; Roel Vermeulen; Ole Raaschou-Nielsen; Gianluca Campanella; Gerard Hoek; Soterios Kyrtopoulos; Panagiotis Georgiadis; Alessio Naccarati; Carlotta Sacerdote; Vittorio Krogh; H. Bas Bueno-De-Mesquita; W.M. Monique Verschuren; Sergi Sayols Baixeras; Tommaso Panni; Annette Peters; Dennie Hebels; Jos Kleinjans; Paolo Vineis; Marc Chadeau-Hyam. 2017. "DNA methylation and exposure to ambient air pollution in two prospective cohorts." Environment International 108, no. : 127-136.

Journal article
Published: 23 August 2017 in Scientific Reports
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Persistent organic pollutants (POPs) are synthetic chemical substances that accumulate in our environment. POPs such as polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB) and dichlorodiphenyltrichloroethane (DDT) have been classified as carcinogenic to humans and animals. Due to their resistance to biodegradation humans are still exposed to these compounds worldwide. We aim to evaluate the miRNA and transcriptomic response of a human population exposed to POPs. The miRNA and transcriptomic response was measured in blood of healthy subjects by microarray technology and associated with the serum concentrations of six PCB congeners, DDE (a common DDT metabolite), and HCB. A total of 93 miRNA levels appeared significantly associated with the POP-exposure (FDR < 0.05). The miRNA profile includes four tumor suppressor miRNAs, namely miR-193a-3p, miR-152, miR-31-5p and miR-34a-5p. Integration of the miRNA profile with the transcriptome profile suggests an interaction with oncogenes such as MYC, CCND1, BCL2 and VEGFA. We have shown that exposure to POPs is associated with human miRNA and transcriptomic responses. The identified miRNAs and target genes are related to various types of cancer and involved in relevant signaling pathways like wnt and p53. Therefore, these miRNAs may have great potential to contribute to biomarker-based environmental health risk assessment.

ACS Style

Julian Krauskopf; Theo M. De Kok; Dennie Hebels; Ingvar A. Bergdahl; Anders Johansson; Florentin Spaeth; Hannu Kiviranta; Panu Rantakokko; Soterios Kyrtopoulos; Jos C. Kleinjans. MicroRNA profile for health risk assessment: Environmental exposure to persistent organic pollutants strongly affects the human blood microRNA machinery. Scientific Reports 2017, 7, 1 -9.

AMA Style

Julian Krauskopf, Theo M. De Kok, Dennie Hebels, Ingvar A. Bergdahl, Anders Johansson, Florentin Spaeth, Hannu Kiviranta, Panu Rantakokko, Soterios Kyrtopoulos, Jos C. Kleinjans. MicroRNA profile for health risk assessment: Environmental exposure to persistent organic pollutants strongly affects the human blood microRNA machinery. Scientific Reports. 2017; 7 (1):1-9.

Chicago/Turabian Style

Julian Krauskopf; Theo M. De Kok; Dennie Hebels; Ingvar A. Bergdahl; Anders Johansson; Florentin Spaeth; Hannu Kiviranta; Panu Rantakokko; Soterios Kyrtopoulos; Jos C. Kleinjans. 2017. "MicroRNA profile for health risk assessment: Environmental exposure to persistent organic pollutants strongly affects the human blood microRNA machinery." Scientific Reports 7, no. 1: 1-9.

Journal article
Published: 23 May 2017 in Human Molecular Genetics
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Lifestyle factors, such as food choices and exposure to chemicals, can alter DNA methylation and lead to changes in gene activity. Two such exposures with pharmacologically active components are coffee and tea consumption. Both coffee and tea have been suggested to play an important role in modulating disease-risk in humans by suppressing tumour progression, decreasing inflammation and influencing estrogen metabolism. These mechanisms may be mediated by changes in DNA methylation. To investigate if DNA methylation in blood is associated with coffee and tea consumption, we performed a genome-wide DNA methylation study for coffee and tea consumption in four European cohorts (N = 3,096). DNA methylation was measured from whole blood at 421,695 CpG sites distributed throughout the genome and analysed in men and women both separately and together in each cohort. Meta-analyses of the results and additional regional-level analyses were performed. After adjusting for multiple testing, the meta-analysis revealed that two individual CpG-sites, mapping to DNAJC16 and TTC17, were differentially methylated in relation to tea consumption in women. No individual sites were associated with men or with the sex-combined analysis for tea or coffee. The regional analysis revealed that 28 regions were differentially methylated in relation to tea consumption in women. These regions contained genes known to interact with estradiol metabolism and cancer. No significant regions were found in the sex-combined and male-only analysis for either tea or coffee consumption.

ACS Style

Weronica E. Ek; Elmar W. Tobi; Muhammad Ahsan; Erik Lampa; Erica Ponzi; Soterios A. Kyrtopoulos; Panagiotis Georgiadis; L.H. Lumey; Bastiaan T. Heijmans; Maria Botsivali; Ingvar A. Bergdahl; Torgny Karlsson; Mathias Rask-Andersen; Domenico Palli; Erik Ingelsson; Åsa K. Hedman; Lena M. Nilsson; Paolo Vineis; Lars Lind; James M. Flanagan; Åsa Johansson; on behalf of the Epigenome-Wide Association Study Consortium. Tea and coffee consumption in relation to DNA methylation in four European cohorts. Human Molecular Genetics 2017, 26, 3221 -3231.

AMA Style

Weronica E. Ek, Elmar W. Tobi, Muhammad Ahsan, Erik Lampa, Erica Ponzi, Soterios A. Kyrtopoulos, Panagiotis Georgiadis, L.H. Lumey, Bastiaan T. Heijmans, Maria Botsivali, Ingvar A. Bergdahl, Torgny Karlsson, Mathias Rask-Andersen, Domenico Palli, Erik Ingelsson, Åsa K. Hedman, Lena M. Nilsson, Paolo Vineis, Lars Lind, James M. Flanagan, Åsa Johansson, on behalf of the Epigenome-Wide Association Study Consortium. Tea and coffee consumption in relation to DNA methylation in four European cohorts. Human Molecular Genetics. 2017; 26 (16):3221-3231.

Chicago/Turabian Style

Weronica E. Ek; Elmar W. Tobi; Muhammad Ahsan; Erik Lampa; Erica Ponzi; Soterios A. Kyrtopoulos; Panagiotis Georgiadis; L.H. Lumey; Bastiaan T. Heijmans; Maria Botsivali; Ingvar A. Bergdahl; Torgny Karlsson; Mathias Rask-Andersen; Domenico Palli; Erik Ingelsson; Åsa K. Hedman; Lena M. Nilsson; Paolo Vineis; Lars Lind; James M. Flanagan; Åsa Johansson; on behalf of the Epigenome-Wide Association Study Consortium. 2017. "Tea and coffee consumption in relation to DNA methylation in four European cohorts." Human Molecular Genetics 26, no. 16: 3221-3231.

Journal article
Published: 01 May 2017 in Epidemiology
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This study provides evidence of subtle changes in gene expression related to exposure to long-term NOx. On a global level, the observed changes in the transcriptome may indicate similarities between air pollution and tobacco induced changes in the transcriptome.

ACS Style

Nahid Mostafavi; Jelle Vlaanderen; Lutzen Portengen; Marc Chadeau-Hyam; Lars Modig; Domenico Palli; Ingvar A. Bergdahl; Bert Brunekreef; Paolo Vineis; Dennie G. A. J. Hebels; Jos C. S. Kleinjans; Vittorio Krogh; Gerard Hoek; Panagiotis Georgiadis; Soterios . Kyrtopoulos; Roel Vermeulen. Associations Between Genome-wide Gene Expression and Ambient Nitrogen Oxides. Epidemiology 2017, 28, 320 -328.

AMA Style

Nahid Mostafavi, Jelle Vlaanderen, Lutzen Portengen, Marc Chadeau-Hyam, Lars Modig, Domenico Palli, Ingvar A. Bergdahl, Bert Brunekreef, Paolo Vineis, Dennie G. A. J. Hebels, Jos C. S. Kleinjans, Vittorio Krogh, Gerard Hoek, Panagiotis Georgiadis, Soterios . Kyrtopoulos, Roel Vermeulen. Associations Between Genome-wide Gene Expression and Ambient Nitrogen Oxides. Epidemiology. 2017; 28 (3):320-328.

Chicago/Turabian Style

Nahid Mostafavi; Jelle Vlaanderen; Lutzen Portengen; Marc Chadeau-Hyam; Lars Modig; Domenico Palli; Ingvar A. Bergdahl; Bert Brunekreef; Paolo Vineis; Dennie G. A. J. Hebels; Jos C. S. Kleinjans; Vittorio Krogh; Gerard Hoek; Panagiotis Georgiadis; Soterios . Kyrtopoulos; Roel Vermeulen. 2017. "Associations Between Genome-wide Gene Expression and Ambient Nitrogen Oxides." Epidemiology 28, no. 3: 320-328.

Journal article
Published: 20 March 2017 in BMC Genomics
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We recently identified 700 genes whose expression levels were predictive of chronic lymphocytic leukemia (CLL) in a genome-wide gene expression analysis of prediagnostic blood from future cases and matched controls. We hypothesized that a large fraction of these markers were likely related to early disease manifestations. Here we aim to gain a better understanding of the natural history of the identified markers by comparing results from our prediagnostic analysis, the only prediagnostic analysis to date, to results obtained from a meta-analysis of a series of publically available transcriptomics profiles obtained in incident CLL cases and controls. We observed considerable overlap between the results from our prediagnostic study and the clinical CLL signals (p-value for overlap Bonferroni significant markers 0.01; p-value for overlap nominal significant markers < 2.20e-16). We observed similar patterns with time to diagnosis and similar functional annotations for the markers that were identified in both settings compared to the markers that were only identified in the prediagnostic study. These results suggest that both gene sets operate in similar pathways. An overlap exists between expression levels of genes predictive of CLL identified in prediagnostic blood and expression levels of genes associated to CLL at the clinical stage. Our analysis provides insight in a set of genes for which expression levels can be used to follow the time-course of the disease; providing an opportunity to study CLL progression in more detail in future studies.

ACS Style

Jelle Vlaanderen; Max Leenders; Marc Chadeau-Hyam; Lützen Portengen; Soterios A. Kyrtopoulos; Ingvar A. Bergdahl; Ann-Sofie Johansson; Dennie Hebels; Theo M.C.M. De Kok; Paolo Vineis; Roel C.H. Vermeulen. Exploring the nature of prediagnostic blood transcriptome markers of chronic lymphocytic leukemia by assessing their overlap with the transcriptome at the clinical stage. BMC Genomics 2017, 18, 239 .

AMA Style

Jelle Vlaanderen, Max Leenders, Marc Chadeau-Hyam, Lützen Portengen, Soterios A. Kyrtopoulos, Ingvar A. Bergdahl, Ann-Sofie Johansson, Dennie Hebels, Theo M.C.M. De Kok, Paolo Vineis, Roel C.H. Vermeulen. Exploring the nature of prediagnostic blood transcriptome markers of chronic lymphocytic leukemia by assessing their overlap with the transcriptome at the clinical stage. BMC Genomics. 2017; 18 (1):239.

Chicago/Turabian Style

Jelle Vlaanderen; Max Leenders; Marc Chadeau-Hyam; Lützen Portengen; Soterios A. Kyrtopoulos; Ingvar A. Bergdahl; Ann-Sofie Johansson; Dennie Hebels; Theo M.C.M. De Kok; Paolo Vineis; Roel C.H. Vermeulen. 2017. "Exploring the nature of prediagnostic blood transcriptome markers of chronic lymphocytic leukemia by assessing their overlap with the transcriptome at the clinical stage." BMC Genomics 18, no. 1: 239.

Journal article
Published: 07 March 2017 in The FASEB Journal
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Exposure to environmental stressors, toxicants, and nutrient deficiencies can affect DNA in several ways. Some exposures cause damage and alter the structure of DNA, but there is increasing evidence that the same or other environmental exposures, including those that occur during fetal development in utero, can cause epigenetic effects that modulate DNA function and gene expression. Some epigenetic changes to DNA that affect gene transcription are at least partially reversible (i.e., they can be enzymatically reversed after cessation of exposure to environmental agents), but some epigenetic modifications seem to persist, even for decades. To explain the effects of early life experiences (such as famine and exposures to other stressors) on the long-term persistence of specific patterns of epigenetic modifications, such as DNA methylation, we propose an analogy with immune memory. We propose that an epigenetic memory can be established and maintained in self-renewing stem cell compartments. We suggest that the observations on early life effects on adult diseases and the persistence of methylation changes in smokers support our hypothesis, for which a mechanistic basis, however, needs to be further clarified. We outline a new model based on methylation changes. Although these changes seem to be mainly adaptive, they are also implicated in the pathogenesis and onset of diseases, depending on individual genotypic background and types of subsequent exposures. Elucidating the relationships between the adaptive and maladaptive consequences of the epigenetic modifications that result from complex environmental exposures is a major challenge for current and future research in epigenetics.—Vineis, P., Chatziioannou, A., Cunliffe, V. T., Flanagan, J. M., Hanson, M., Kirsch-Volders, M., Kyrtopoulos, S. Epigenetic memory in response to environmental stressors.

ACS Style

Paolo Vineis; Aristotelis Chatziioannou; Vincent T. Cunliffe; James M. Flanagan; Mark Hanson; Micheline Kirsch‐Volders; Soterios Kyrtopoulos. Epigenetic memory in response to environmental stressors. The FASEB Journal 2017, 31, 2241 -2251.

AMA Style

Paolo Vineis, Aristotelis Chatziioannou, Vincent T. Cunliffe, James M. Flanagan, Mark Hanson, Micheline Kirsch‐Volders, Soterios Kyrtopoulos. Epigenetic memory in response to environmental stressors. The FASEB Journal. 2017; 31 (6):2241-2251.

Chicago/Turabian Style

Paolo Vineis; Aristotelis Chatziioannou; Vincent T. Cunliffe; James M. Flanagan; Mark Hanson; Micheline Kirsch‐Volders; Soterios Kyrtopoulos. 2017. "Epigenetic memory in response to environmental stressors." The FASEB Journal 31, no. 6: 2241-2251.

Journal article
Published: 22 February 2017 in Scientific Reports
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We recently reported that differential gene expression and DNA methylation profiles in blood leukocytes of apparently healthy smokers predicts with remarkable efficiency diseases and conditions known to be causally associated with smoking, suggesting that blood-based omic profiling of human populations may be useful for linking environmental exposures to potential health effects. Here we report on the sex-specific effects of tobacco smoking on transcriptomic and epigenetic features derived from genome-wide profiling in white blood cells, identifying 26 expression probes and 92 CpG sites, almost all of which are affected only in female smokers. Strikingly, these features relate to numerous genes with a key role in the pathogenesis of cardiovascular disease, especially thrombin signaling, including the thrombin receptors on platelets F2R (coagulation factor II (thrombin) receptor; PAR1) and GP5 (glycoprotein 5), as well as HMOX1 (haem oxygenase 1) and BCL2L1 (BCL2-like 1) which are involved in protection against oxidative stress and apoptosis, respectively. These results are in concordance with epidemiological evidence of higher female susceptibility to tobacco-induced cardiovascular disease and underline the potential of blood-based omic profiling in hazard and risk assessment.

ACS Style

Aristotelis Chatziioannou; The EnviroGenomarkers project consortium; Panagiotis Georgiadis; Dennie Hebels; Irene Liampa; Ioannis Valavanis; Ingvar A. Bergdahl; Anders Johansson; Menico Palli; Marc Chadeau-Hyam; Alexandros Siskos; Hector Keun; Maria Botsivali; Theo M. C. M. De Kok; Almudena Espín Pérez; Jos C. S. Kleinjans; Paolo Vineis; Soterios A. Kyrtopoulos; Ralph Gottschalk. Blood-based omic profiling supports female susceptibility to tobacco smoke-induced cardiovascular diseases. Scientific Reports 2017, 7, 42870 .

AMA Style

Aristotelis Chatziioannou, The EnviroGenomarkers project consortium, Panagiotis Georgiadis, Dennie Hebels, Irene Liampa, Ioannis Valavanis, Ingvar A. Bergdahl, Anders Johansson, Menico Palli, Marc Chadeau-Hyam, Alexandros Siskos, Hector Keun, Maria Botsivali, Theo M. C. M. De Kok, Almudena Espín Pérez, Jos C. S. Kleinjans, Paolo Vineis, Soterios A. Kyrtopoulos, Ralph Gottschalk. Blood-based omic profiling supports female susceptibility to tobacco smoke-induced cardiovascular diseases. Scientific Reports. 2017; 7 (1):42870.

Chicago/Turabian Style

Aristotelis Chatziioannou; The EnviroGenomarkers project consortium; Panagiotis Georgiadis; Dennie Hebels; Irene Liampa; Ioannis Valavanis; Ingvar A. Bergdahl; Anders Johansson; Menico Palli; Marc Chadeau-Hyam; Alexandros Siskos; Hector Keun; Maria Botsivali; Theo M. C. M. De Kok; Almudena Espín Pérez; Jos C. S. Kleinjans; Paolo Vineis; Soterios A. Kyrtopoulos; Ralph Gottschalk. 2017. "Blood-based omic profiling supports female susceptibility to tobacco smoke-induced cardiovascular diseases." Scientific Reports 7, no. 1: 42870.

Research
Published: 16 February 2017 in Environmental Health
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Evidence suggests a largely environmental component to non-Hodgkin’s lymphoma (NHL). Persistent organic pollutants (POPs) including polychlorinated biphenyls (PCBs), DDE and HCB have been repeatedly implicated, but the literature is inconsistent and a causal relationship remains to be determined. The EnviroGenoMarkers study is nested within two prospective cohorts EPIC-Italy and the Northern Sweden Health and Disease Study. Six PCB congeners, DDE and HCB were measured in blood plasma samples provided at recruitment using gas-chromatography mass spectrometry. During 16 years follow-up 270 incident cases of B-cell NHL (including 76 cases of multiple myeloma) were diagnosed. Cases were matched to 270 healthy controls by centre, age, gender and date of blood collection. Cases were categorised into ordered quartiles of exposure for each POP based on the distribution of exposure in the control population. Logistic regression was applied to assess the association with risk, multivariate and stratified analyses were performed to identify confounders or effect modifiers. The exposures displayed a strong degree of correlation, particularly amongst those PCBs with similar degrees of chlorination. There was no significant difference (p < 0.05) in median exposure levels between cases and controls for any of the investigated exposures. However under a multivariate model PCB138, PCB153, HCB and DDE displayed significant inverse trends (Wald test p-value 90th percentile) the association was null for all POPs We report no evidence that a higher body burden of PCBs, DDE or HCB increased the risk of subsequent NHL diagnosis. Significantly inverse associations were noted for males with a number of the investigated POPs. We hypothesize these unexpected relationships may relate to the subtype composition of our population, effect modification by BMI or other unmeasured confounding. This study provides no additional support for the previously observed role of PCBs, DDE and HCB as risk factors for NHL.

ACS Style

Rachel S. Kelly; on behalf of the EnviroGenoMarkers project consortium; Hannu Kiviranta; Ingvar A. Bergdahl; Domenico Palli; Ann-Sofie Johansson; Maria Botsivali; Paolo Vineis; Roel Vermeulen; Soterios A. Kyrtopoulos; Marc Chadeau-Hyam. Prediagnostic plasma concentrations of organochlorines and risk of B-cell non-Hodgkin lymphoma in envirogenomarkers: a nested case-control study. Environmental Health 2017, 16, 1 -12.

AMA Style

Rachel S. Kelly, on behalf of the EnviroGenoMarkers project consortium, Hannu Kiviranta, Ingvar A. Bergdahl, Domenico Palli, Ann-Sofie Johansson, Maria Botsivali, Paolo Vineis, Roel Vermeulen, Soterios A. Kyrtopoulos, Marc Chadeau-Hyam. Prediagnostic plasma concentrations of organochlorines and risk of B-cell non-Hodgkin lymphoma in envirogenomarkers: a nested case-control study. Environmental Health. 2017; 16 (1):1-12.

Chicago/Turabian Style

Rachel S. Kelly; on behalf of the EnviroGenoMarkers project consortium; Hannu Kiviranta; Ingvar A. Bergdahl; Domenico Palli; Ann-Sofie Johansson; Maria Botsivali; Paolo Vineis; Roel Vermeulen; Soterios A. Kyrtopoulos; Marc Chadeau-Hyam. 2017. "Prediagnostic plasma concentrations of organochlorines and risk of B-cell non-Hodgkin lymphoma in envirogenomarkers: a nested case-control study." Environmental Health 16, no. 1: 1-12.

Clinical trial
Published: 09 December 2016 in Scientific Reports
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Consistent evidence is accumulating to link lower socioeconomic position (SEP) and poorer health, and the inflammatory system stands out as a potential pathway through which socioeconomic environment is biologically embedded. Using bloodderived genome-wide transcriptional profiles from 268 Italian participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we evaluated the association between early life, young and later adulthood SEP and the expression of 845 genes involved in human inflammatory responses. These were examined individually and jointly using several inflammatory scores. Our results consistently show that participants whose father had a manual (as compared to nonmanual) occupation exhibit, later in life, a higher inflammatory score, hence indicating an overall increased level of expression for the selected inflammatory-related genes. Adopting a life course approach, these associations remained statistically significant upon adjustment for later-in-life socioeconomic experiences. Sensitivity analyses indicated that our findings were not affected by the way the inflammatory score was calculated, and were replicated in an independent study. Our study provides additional evidence that childhood SEP is associated with a sustainable upregulation of the inflammatory transcriptome, independently of subsequent socioeconomic experiences. Our results support the hypothesis that early social inequalities impacts adult physiology.

ACS Style

Raphaele Castagne; Michelle Kelly-Irving; Gianluca Campanella; Florence Guida; Vittorio Krogh; Domenico Palli; Salvatore Panico; Carlotta Sacerdote; Rosario Tumino; Jos Kleinjans; Theo De Kok; Soterios Kyrtopoulos; Thierry Lang; Silvia Stringhini; Roel Vermeulen; Paolo Vineis; Cyrille Delpierre; Marc Chadeau-Hyam. Biological marks of early-life socioeconomic experience is detected in the adult inflammatory transcriptome. Scientific Reports 2016, 6, 38705 .

AMA Style

Raphaele Castagne, Michelle Kelly-Irving, Gianluca Campanella, Florence Guida, Vittorio Krogh, Domenico Palli, Salvatore Panico, Carlotta Sacerdote, Rosario Tumino, Jos Kleinjans, Theo De Kok, Soterios Kyrtopoulos, Thierry Lang, Silvia Stringhini, Roel Vermeulen, Paolo Vineis, Cyrille Delpierre, Marc Chadeau-Hyam. Biological marks of early-life socioeconomic experience is detected in the adult inflammatory transcriptome. Scientific Reports. 2016; 6 (1):38705.

Chicago/Turabian Style

Raphaele Castagne; Michelle Kelly-Irving; Gianluca Campanella; Florence Guida; Vittorio Krogh; Domenico Palli; Salvatore Panico; Carlotta Sacerdote; Rosario Tumino; Jos Kleinjans; Theo De Kok; Soterios Kyrtopoulos; Thierry Lang; Silvia Stringhini; Roel Vermeulen; Paolo Vineis; Cyrille Delpierre; Marc Chadeau-Hyam. 2016. "Biological marks of early-life socioeconomic experience is detected in the adult inflammatory transcriptome." Scientific Reports 6, no. 1: 38705.