Confirmation of childhood acute lymphoblastic leukemia variants, ARID5B and IKZF1, and interaction with parental environmental exposures.
Identifieur interne : 003729 ( PubMed/Checkpoint ); précédent : 003728; suivant : 003730Confirmation of childhood acute lymphoblastic leukemia variants, ARID5B and IKZF1, and interaction with parental environmental exposures.
Auteurs : Tiffany-Jane Evans [Australie] ; Elizabeth Milne [Australie] ; Denise Anderson [Australie] ; Nicholas H. De Klerk [Australie] ; Sarra E. Jamieson [Australie] ; Bente A. Talseth-Palmer [Australie] ; Nikola A. Bowden [Australie] ; Elizabeth G. Holliday [Australie] ; Jérémie Rudant [France] ; Laurent Orsi [France] ; Ebony Richardson [Australie] ; Laura Lavis [Australie] ; Daniel Catchpoole [Australie] ; John R. Attia [Australie] ; Bruce K. Armstrong [Australie] ; Jacqueline Clavel [France] ; Rodney J. Scott [Australie]Source :
- PloS one [ 1932-6203 ] ; 2014.
Descripteurs français
- KwdFr :
- Adulte, Enfant, Exposition environnementale, Facteur de transcription Ikaros (génétique), Facteurs de transcription (génétique), Femelle, Humains, Interaction entre gènes et environnement, Leucémie-lymphome lymphoblastique à précurseurs B et T (génétique), Mâle, Parents, Polymorphisme de nucléotide simple (génétique), Protéines de liaison à l'ADN (génétique), Reproductibilité des résultats, Étude d'association pangénomique.
- MESH :
- génétique : Facteur de transcription Ikaros, Facteurs de transcription, Leucémie-lymphome lymphoblastique à précurseurs B et T, Polymorphisme de nucléotide simple, Protéines de liaison à l'ADN.
- Adulte, Enfant, Exposition environnementale, Femelle, Humains, Interaction entre gènes et environnement, Mâle, Parents, Reproductibilité des résultats, Étude d'association pangénomique.
English descriptors
- KwdEn :
- Adult, Child, DNA-Binding Proteins (genetics), Environmental Exposure, Female, Gene-Environment Interaction, Genome-Wide Association Study, Humans, Ikaros Transcription Factor (genetics), Male, Parents, Polymorphism, Single Nucleotide (genetics), Precursor Cell Lymphoblastic Leukemia-Lymphoma (genetics), Reproducibility of Results, Transcription Factors (genetics).
- MESH :
- chemical , genetics : DNA-Binding Proteins, Ikaros Transcription Factor, Transcription Factors.
- genetics : Polymorphism, Single Nucleotide, Precursor Cell Lymphoblastic Leukemia-Lymphoma.
- Adult, Child, Environmental Exposure, Female, Gene-Environment Interaction, Genome-Wide Association Study, Humans, Male, Parents, Reproducibility of Results.
Abstract
Genome wide association studies (GWAS) have established association of ARID5B and IKZF1 variants with childhood acute lymphoblastic leukemia (ALL). Epidemiological studies suggest that environmental factors alone appear to make a relatively minor contribution to disease risk. The polygenic nature of childhood ALL predisposition together with the timing of environmental triggers may hold vital clues for disease etiology. This study presents results from an Australian GWAS of childhood ALL cases (n = 358) and population controls (n = 1192). Furthermore, we utilised family trio (n = 204) genotypes to extend our investigation to gene-environment interaction of significant loci with parental exposures before conception, and child's sex and age. Thirteen SNPs achieved genome wide significance in the population based case/control analysis; ten annotated to ARID5B and three to IKZF1. The most significant SNPs in these regions were ARID5B rs4245595 (OR 1.63, CI 1.38-1.93, P = 2.13×10(-9)), and IKZF1 rs1110701 (OR 1.69, CI 1.42-2.02, p = 7.26×10(-9)). There was evidence of gene-environment interaction for risk genotype at IKZF1, whereby an apparently stronger genetic effect was observed if the mother took folic acid or if the father did not smoke prior to pregnancy (respective interaction P-values: 0.04, 0.05). There were no interactions of risk genotypes with age or sex (P-values >0.2). Our results evidence that interaction of genetic variants and environmental exposures may further alter risk of childhood ALL however, investigation in a larger population is required. If interaction of folic acid supplementation and IKZF1 variants holds, it may be useful to quantify folate levels prior to initiating use of folic acid supplements.
DOI: 10.1371/journal.pone.0110255
PubMed: 25310577
Affiliations:
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Bowden</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Bioinformatics, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia; School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Centre for Bioinformatics, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia; School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales</wicri:regionArea><wicri:noRegion>New South Wales</wicri:noRegion></affiliation></author><author><name sortKey="Holliday, Elizabeth G" sort="Holliday, Elizabeth G" uniqKey="Holliday E" first="Elizabeth G" last="Holliday">Elizabeth G. Holliday</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Bioinformatics, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia; Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Centre for Bioinformatics, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia; Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales</wicri:regionArea><wicri:noRegion>New South Wales</wicri:noRegion></affiliation></author><author><name sortKey="Rudant, Jeremie" sort="Rudant, Jeremie" uniqKey="Rudant J" first="Jérémie" last="Rudant">Jérémie Rudant</name><affiliation wicri:level="1"><nlm:affiliation>INSERM, U1018, Department of Environmental Epidemiology of Cancers, Villejuif, France; Paris-Sud University, UMR-S1018, Department of Environmental Epidemiology of Cancers, Research Center in Epidemiology and Population Health, Villejuif, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, U1018, Department of Environmental Epidemiology of Cancers, Villejuif, France; Paris-Sud University, UMR-S1018, Department of Environmental Epidemiology of Cancers, Research Center in Epidemiology and Population Health, Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation></author><author><name sortKey="Orsi, Laurent" sort="Orsi, Laurent" uniqKey="Orsi L" first="Laurent" last="Orsi">Laurent Orsi</name><affiliation wicri:level="1"><nlm:affiliation>INSERM, U1018, Department of Environmental Epidemiology of Cancers, Villejuif, France; Paris-Sud University, UMR-S1018, Department of Environmental Epidemiology of Cancers, Research Center in Epidemiology and Population Health, Villejuif, France; French National Registry of Childhood Blood Malignancies (RNHE), Villejuif, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, U1018, Department of Environmental Epidemiology of Cancers, Villejuif, France; Paris-Sud University, UMR-S1018, Department of Environmental Epidemiology of Cancers, Research Center in Epidemiology and Population Health, Villejuif, France; French National Registry of Childhood Blood Malignancies (RNHE), Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation></author><author><name sortKey="Richardson, Ebony" sort="Richardson, Ebony" uniqKey="Richardson E" first="Ebony" last="Richardson">Ebony Richardson</name><affiliation wicri:level="1"><nlm:affiliation>School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales</wicri:regionArea><wicri:noRegion>New South Wales</wicri:noRegion></affiliation></author><author><name sortKey="Lavis, Laura" sort="Lavis, Laura" uniqKey="Lavis L" first="Laura" last="Lavis">Laura Lavis</name><affiliation wicri:level="1"><nlm:affiliation>School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales</wicri:regionArea><wicri:noRegion>New South Wales</wicri:noRegion></affiliation></author><author><name sortKey="Catchpoole, Daniel" sort="Catchpoole, Daniel" uniqKey="Catchpoole D" first="Daniel" last="Catchpoole">Daniel Catchpoole</name><affiliation wicri:level="1"><nlm:affiliation>The Tumour Bank, The Children's Cancer Research Unit, The Children's Hospital Westmead, Westmead, New South Wales, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>The Tumour Bank, The Children's Cancer Research Unit, The Children's Hospital Westmead, Westmead, New South Wales</wicri:regionArea><wicri:noRegion>New South Wales</wicri:noRegion></affiliation></author><author><name sortKey="Attia, John R" sort="Attia, John R" uniqKey="Attia J" first="John R" last="Attia">John R. Attia</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Bioinformatics, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia; Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia; Department of Medicine, John Hunter Hospital and Hunter Medical Research Institute, New Lambton, New South Wales, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Centre for Bioinformatics, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia; Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia; Department of Medicine, John Hunter Hospital and Hunter Medical Research Institute, New Lambton, New South Wales</wicri:regionArea><wicri:noRegion>New South Wales</wicri:noRegion></affiliation></author><author><name sortKey="Armstrong, Bruce K" sort="Armstrong, Bruce K" uniqKey="Armstrong B" first="Bruce K" last="Armstrong">Bruce K. Armstrong</name><affiliation wicri:level="1"><nlm:affiliation>School of Public Health, The University of Sydney and Sax Institute, Sydney, New South Wales, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Public Health, The University of Sydney and Sax Institute, Sydney, New South Wales</wicri:regionArea><wicri:noRegion>New South Wales</wicri:noRegion></affiliation></author><author><name sortKey="Clavel, Jacqueline" sort="Clavel, Jacqueline" uniqKey="Clavel J" first="Jacqueline" last="Clavel">Jacqueline Clavel</name><affiliation wicri:level="1"><nlm:affiliation>INSERM, U1018, Department of Environmental Epidemiology of Cancers, Villejuif, France; Paris-Sud University, UMR-S1018, Department of Environmental Epidemiology of Cancers, Research Center in Epidemiology and Population Health, Villejuif, France; French National Registry of Childhood Blood Malignancies (RNHE), Villejuif, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, U1018, Department of Environmental Epidemiology of Cancers, Villejuif, France; Paris-Sud University, UMR-S1018, Department of Environmental Epidemiology of Cancers, Research Center in Epidemiology and Population Health, Villejuif, France; French National Registry of Childhood Blood Malignancies (RNHE), Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation></author><author><name sortKey="Scott, Rodney J" sort="Scott, Rodney J" uniqKey="Scott R" first="Rodney J" last="Scott">Rodney J. Scott</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Bioinformatics, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia; School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia; Molecular Genetics, Hunter Area Pathology Service, Newcastle, New South Wales, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Centre for Bioinformatics, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia; School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia; Molecular Genetics, Hunter Area Pathology Service, Newcastle, New South Wales</wicri:regionArea><wicri:noRegion>New South Wales</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:25310577</idno><idno type="pmid">25310577</idno><idno type="doi">10.1371/journal.pone.0110255</idno><idno type="wicri:Area/PubMed/Corpus">003375</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">003375</idno><idno type="wicri:Area/PubMed/Curation">003263</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">003263</idno><idno type="wicri:Area/PubMed/Checkpoint">003263</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">003263</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Confirmation of childhood acute lymphoblastic leukemia variants, ARID5B and IKZF1, and interaction with parental environmental exposures.</title><author><name sortKey="Evans, Tiffany Jane" sort="Evans, Tiffany Jane" uniqKey="Evans T" first="Tiffany-Jane" last="Evans">Tiffany-Jane Evans</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Bioinformatics, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia; School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Centre for Bioinformatics, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia; School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales</wicri:regionArea><wicri:noRegion>New South Wales</wicri:noRegion></affiliation></author><author><name sortKey="Milne, Elizabeth" sort="Milne, Elizabeth" uniqKey="Milne E" first="Elizabeth" last="Milne">Elizabeth Milne</name><affiliation wicri:level="1"><nlm:affiliation>Telethon Kids Institute, The University of Western Australia, Perth, Western Australia, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Telethon Kids Institute, The University of Western Australia, Perth, Western Australia</wicri:regionArea><wicri:noRegion>Western Australia</wicri:noRegion></affiliation></author><author><name sortKey="Anderson, Denise" sort="Anderson, Denise" uniqKey="Anderson D" first="Denise" last="Anderson">Denise Anderson</name><affiliation wicri:level="1"><nlm:affiliation>Telethon Kids Institute, The University of Western Australia, Perth, Western Australia, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Telethon Kids Institute, The University of Western Australia, Perth, Western Australia</wicri:regionArea><wicri:noRegion>Western Australia</wicri:noRegion></affiliation></author><author><name sortKey="De Klerk, Nicholas H" sort="De Klerk, Nicholas H" uniqKey="De Klerk N" first="Nicholas H" last="De Klerk">Nicholas H. De Klerk</name><affiliation wicri:level="1"><nlm:affiliation>Telethon Kids Institute, The University of Western Australia, Perth, Western Australia, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Telethon Kids Institute, The University of Western Australia, Perth, Western Australia</wicri:regionArea><wicri:noRegion>Western Australia</wicri:noRegion></affiliation></author><author><name sortKey="Jamieson, Sarra E" sort="Jamieson, Sarra E" uniqKey="Jamieson S" first="Sarra E" last="Jamieson">Sarra E. Jamieson</name><affiliation wicri:level="1"><nlm:affiliation>Telethon Kids Institute, The University of Western Australia, Perth, Western Australia, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Telethon Kids Institute, The University of Western Australia, Perth, Western Australia</wicri:regionArea><wicri:noRegion>Western Australia</wicri:noRegion></affiliation></author><author><name sortKey="Talseth Palmer, Bente A" sort="Talseth Palmer, Bente A" uniqKey="Talseth Palmer B" first="Bente A" last="Talseth-Palmer">Bente A. Talseth-Palmer</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Bioinformatics, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia; School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Centre for Bioinformatics, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia; School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales</wicri:regionArea><wicri:noRegion>New South Wales</wicri:noRegion></affiliation></author><author><name sortKey="Bowden, Nikola A" sort="Bowden, Nikola A" uniqKey="Bowden N" first="Nikola A" last="Bowden">Nikola A. Bowden</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Bioinformatics, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia; School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Centre for Bioinformatics, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia; School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales</wicri:regionArea><wicri:noRegion>New South Wales</wicri:noRegion></affiliation></author><author><name sortKey="Holliday, Elizabeth G" sort="Holliday, Elizabeth G" uniqKey="Holliday E" first="Elizabeth G" last="Holliday">Elizabeth G. Holliday</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Bioinformatics, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia; Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Centre for Bioinformatics, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia; Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales</wicri:regionArea><wicri:noRegion>New South Wales</wicri:noRegion></affiliation></author><author><name sortKey="Rudant, Jeremie" sort="Rudant, Jeremie" uniqKey="Rudant J" first="Jérémie" last="Rudant">Jérémie Rudant</name><affiliation wicri:level="1"><nlm:affiliation>INSERM, U1018, Department of Environmental Epidemiology of Cancers, Villejuif, France; Paris-Sud University, UMR-S1018, Department of Environmental Epidemiology of Cancers, Research Center in Epidemiology and Population Health, Villejuif, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, U1018, Department of Environmental Epidemiology of Cancers, Villejuif, France; Paris-Sud University, UMR-S1018, Department of Environmental Epidemiology of Cancers, Research Center in Epidemiology and Population Health, Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation></author><author><name sortKey="Orsi, Laurent" sort="Orsi, Laurent" uniqKey="Orsi L" first="Laurent" last="Orsi">Laurent Orsi</name><affiliation wicri:level="1"><nlm:affiliation>INSERM, U1018, Department of Environmental Epidemiology of Cancers, Villejuif, France; Paris-Sud University, UMR-S1018, Department of Environmental Epidemiology of Cancers, Research Center in Epidemiology and Population Health, Villejuif, France; French National Registry of Childhood Blood Malignancies (RNHE), Villejuif, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, U1018, Department of Environmental Epidemiology of Cancers, Villejuif, France; Paris-Sud University, UMR-S1018, Department of Environmental Epidemiology of Cancers, Research Center in Epidemiology and Population Health, Villejuif, France; French National Registry of Childhood Blood Malignancies (RNHE), Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation></author><author><name sortKey="Richardson, Ebony" sort="Richardson, Ebony" uniqKey="Richardson E" first="Ebony" last="Richardson">Ebony Richardson</name><affiliation wicri:level="1"><nlm:affiliation>School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales</wicri:regionArea><wicri:noRegion>New South Wales</wicri:noRegion></affiliation></author><author><name sortKey="Lavis, Laura" sort="Lavis, Laura" uniqKey="Lavis L" first="Laura" last="Lavis">Laura Lavis</name><affiliation wicri:level="1"><nlm:affiliation>School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales</wicri:regionArea><wicri:noRegion>New South Wales</wicri:noRegion></affiliation></author><author><name sortKey="Catchpoole, Daniel" sort="Catchpoole, Daniel" uniqKey="Catchpoole D" first="Daniel" last="Catchpoole">Daniel Catchpoole</name><affiliation wicri:level="1"><nlm:affiliation>The Tumour Bank, The Children's Cancer Research Unit, The Children's Hospital Westmead, Westmead, New South Wales, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>The Tumour Bank, The Children's Cancer Research Unit, The Children's Hospital Westmead, Westmead, New South Wales</wicri:regionArea><wicri:noRegion>New South Wales</wicri:noRegion></affiliation></author><author><name sortKey="Attia, John R" sort="Attia, John R" uniqKey="Attia J" first="John R" last="Attia">John R. Attia</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Bioinformatics, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia; Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia; Department of Medicine, John Hunter Hospital and Hunter Medical Research Institute, New Lambton, New South Wales, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Centre for Bioinformatics, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia; Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia; Department of Medicine, John Hunter Hospital and Hunter Medical Research Institute, New Lambton, New South Wales</wicri:regionArea><wicri:noRegion>New South Wales</wicri:noRegion></affiliation></author><author><name sortKey="Armstrong, Bruce K" sort="Armstrong, Bruce K" uniqKey="Armstrong B" first="Bruce K" last="Armstrong">Bruce K. Armstrong</name><affiliation wicri:level="1"><nlm:affiliation>School of Public Health, The University of Sydney and Sax Institute, Sydney, New South Wales, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Public Health, The University of Sydney and Sax Institute, Sydney, New South Wales</wicri:regionArea><wicri:noRegion>New South Wales</wicri:noRegion></affiliation></author><author><name sortKey="Clavel, Jacqueline" sort="Clavel, Jacqueline" uniqKey="Clavel J" first="Jacqueline" last="Clavel">Jacqueline Clavel</name><affiliation wicri:level="1"><nlm:affiliation>INSERM, U1018, Department of Environmental Epidemiology of Cancers, Villejuif, France; Paris-Sud University, UMR-S1018, Department of Environmental Epidemiology of Cancers, Research Center in Epidemiology and Population Health, Villejuif, France; French National Registry of Childhood Blood Malignancies (RNHE), Villejuif, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, U1018, Department of Environmental Epidemiology of Cancers, Villejuif, France; Paris-Sud University, UMR-S1018, Department of Environmental Epidemiology of Cancers, Research Center in Epidemiology and Population Health, Villejuif, France; French National Registry of Childhood Blood Malignancies (RNHE), Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation></author><author><name sortKey="Scott, Rodney J" sort="Scott, Rodney J" uniqKey="Scott R" first="Rodney J" last="Scott">Rodney J. Scott</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Bioinformatics, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia; School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia; Molecular Genetics, Hunter Area Pathology Service, Newcastle, New South Wales, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Centre for Bioinformatics, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia; School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia; Molecular Genetics, Hunter Area Pathology Service, Newcastle, New South Wales</wicri:regionArea><wicri:noRegion>New South Wales</wicri:noRegion></affiliation></author></analytic><series><title level="j">PloS one</title><idno type="eISSN">1932-6203</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Child</term><term>DNA-Binding Proteins (genetics)</term><term>Environmental Exposure</term><term>Female</term><term>Gene-Environment Interaction</term><term>Genome-Wide Association Study</term><term>Humans</term><term>Ikaros Transcription Factor (genetics)</term><term>Male</term><term>Parents</term><term>Polymorphism, Single Nucleotide (genetics)</term><term>Precursor Cell Lymphoblastic Leukemia-Lymphoma (genetics)</term><term>Reproducibility of Results</term><term>Transcription Factors (genetics)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte</term><term>Enfant</term><term>Exposition environnementale</term><term>Facteur de transcription Ikaros (génétique)</term><term>Facteurs de transcription (génétique)</term><term>Femelle</term><term>Humains</term><term>Interaction entre gènes et environnement</term><term>Leucémie-lymphome lymphoblastique à précurseurs B et T (génétique)</term><term>Mâle</term><term>Parents</term><term>Polymorphisme de nucléotide simple (génétique)</term><term>Protéines de liaison à l'ADN (génétique)</term><term>Reproductibilité des résultats</term><term>Étude d'association pangénomique</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>DNA-Binding Proteins</term><term>Ikaros Transcription Factor</term><term>Transcription Factors</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Polymorphism, Single Nucleotide</term><term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Facteur de transcription Ikaros</term><term>Facteurs de transcription</term><term>Leucémie-lymphome lymphoblastique à précurseurs B et T</term><term>Polymorphisme de nucléotide simple</term><term>Protéines de liaison à l'ADN</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Child</term><term>Environmental Exposure</term><term>Female</term><term>Gene-Environment Interaction</term><term>Genome-Wide Association Study</term><term>Humans</term><term>Male</term><term>Parents</term><term>Reproducibility of Results</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte</term><term>Enfant</term><term>Exposition environnementale</term><term>Femelle</term><term>Humains</term><term>Interaction entre gènes et environnement</term><term>Mâle</term><term>Parents</term><term>Reproductibilité des résultats</term><term>Étude d'association pangénomique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Genome wide association studies (GWAS) have established association of ARID5B and IKZF1 variants with childhood acute lymphoblastic leukemia (ALL). Epidemiological studies suggest that environmental factors alone appear to make a relatively minor contribution to disease risk. The polygenic nature of childhood ALL predisposition together with the timing of environmental triggers may hold vital clues for disease etiology. This study presents results from an Australian GWAS of childhood ALL cases (n = 358) and population controls (n = 1192). Furthermore, we utilised family trio (n = 204) genotypes to extend our investigation to gene-environment interaction of significant loci with parental exposures before conception, and child's sex and age. Thirteen SNPs achieved genome wide significance in the population based case/control analysis; ten annotated to ARID5B and three to IKZF1. The most significant SNPs in these regions were ARID5B rs4245595 (OR 1.63, CI 1.38-1.93, P = 2.13×10(-9)), and IKZF1 rs1110701 (OR 1.69, CI 1.42-2.02, p = 7.26×10(-9)). There was evidence of gene-environment interaction for risk genotype at IKZF1, whereby an apparently stronger genetic effect was observed if the mother took folic acid or if the father did not smoke prior to pregnancy (respective interaction P-values: 0.04, 0.05). There were no interactions of risk genotypes with age or sex (P-values >0.2). Our results evidence that interaction of genetic variants and environmental exposures may further alter risk of childhood ALL however, investigation in a larger population is required. If interaction of folic acid supplementation and IKZF1 variants holds, it may be useful to quantify folate levels prior to initiating use of folic acid supplements.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">25310577</PMID><DateCreated><Year>2014</Year><Month>10</Month><Day>14</Day></DateCreated><DateCompleted><Year>2015</Year><Month>09</Month><Day>17</Day></DateCompleted><DateRevised><Year>2017</Year><Month>02</Month><Day>20</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Electronic">1932-6203</ISSN><JournalIssue CitedMedium="Internet"><Volume>9</Volume><Issue>10</Issue><PubDate><Year>2014</Year></PubDate></JournalIssue><Title>PloS one</Title><ISOAbbreviation>PLoS ONE</ISOAbbreviation></Journal><ArticleTitle>Confirmation of childhood acute lymphoblastic leukemia variants, ARID5B and IKZF1, and interaction with parental environmental exposures.</ArticleTitle><Pagination><MedlinePgn>e110255</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1371/journal.pone.0110255</ELocationID><Abstract><AbstractText>Genome wide association studies (GWAS) have established association of ARID5B and IKZF1 variants with childhood acute lymphoblastic leukemia (ALL). Epidemiological studies suggest that environmental factors alone appear to make a relatively minor contribution to disease risk. The polygenic nature of childhood ALL predisposition together with the timing of environmental triggers may hold vital clues for disease etiology. This study presents results from an Australian GWAS of childhood ALL cases (n = 358) and population controls (n = 1192). Furthermore, we utilised family trio (n = 204) genotypes to extend our investigation to gene-environment interaction of significant loci with parental exposures before conception, and child's sex and age. Thirteen SNPs achieved genome wide significance in the population based case/control analysis; ten annotated to ARID5B and three to IKZF1. The most significant SNPs in these regions were ARID5B rs4245595 (OR 1.63, CI 1.38-1.93, P = 2.13×10(-9)), and IKZF1 rs1110701 (OR 1.69, CI 1.42-2.02, p = 7.26×10(-9)). There was evidence of gene-environment interaction for risk genotype at IKZF1, whereby an apparently stronger genetic effect was observed if the mother took folic acid or if the father did not smoke prior to pregnancy (respective interaction P-values: 0.04, 0.05). There were no interactions of risk genotypes with age or sex (P-values >0.2). Our results evidence that interaction of genetic variants and environmental exposures may further alter risk of childhood ALL however, investigation in a larger population is required. If interaction of folic acid supplementation and IKZF1 variants holds, it may be useful to quantify folate levels prior to initiating use of folic acid supplements.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Evans</LastName><ForeName>Tiffany-Jane</ForeName><Initials>TJ</Initials><AffiliationInfo><Affiliation>Centre for Bioinformatics, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia; School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Milne</LastName><ForeName>Elizabeth</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Telethon Kids Institute, The University of Western Australia, Perth, Western Australia, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Anderson</LastName><ForeName>Denise</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Telethon Kids Institute, The University of Western Australia, Perth, Western Australia, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>de Klerk</LastName><ForeName>Nicholas H</ForeName><Initials>NH</Initials><AffiliationInfo><Affiliation>Telethon Kids Institute, The University of Western Australia, Perth, Western Australia, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jamieson</LastName><ForeName>Sarra E</ForeName><Initials>SE</Initials><AffiliationInfo><Affiliation>Telethon Kids Institute, The University of Western Australia, Perth, Western Australia, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Talseth-Palmer</LastName><ForeName>Bente A</ForeName><Initials>BA</Initials><AffiliationInfo><Affiliation>Centre for Bioinformatics, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia; School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bowden</LastName><ForeName>Nikola A</ForeName><Initials>NA</Initials><AffiliationInfo><Affiliation>Centre for Bioinformatics, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia; School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Holliday</LastName><ForeName>Elizabeth G</ForeName><Initials>EG</Initials><AffiliationInfo><Affiliation>Centre for Bioinformatics, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia; Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rudant</LastName><ForeName>Jérémie</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>INSERM, U1018, Department of Environmental Epidemiology of Cancers, Villejuif, France; Paris-Sud University, UMR-S1018, Department of Environmental Epidemiology of Cancers, Research Center in Epidemiology and Population Health, Villejuif, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Orsi</LastName><ForeName>Laurent</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>INSERM, U1018, Department of Environmental Epidemiology of Cancers, Villejuif, France; Paris-Sud University, UMR-S1018, Department of Environmental Epidemiology of Cancers, Research Center in Epidemiology and Population Health, Villejuif, France; French National Registry of Childhood Blood Malignancies (RNHE), Villejuif, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Richardson</LastName><ForeName>Ebony</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lavis</LastName><ForeName>Laura</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Catchpoole</LastName><ForeName>Daniel</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>The Tumour Bank, The Children's Cancer Research Unit, The Children's Hospital Westmead, Westmead, New South Wales, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Attia</LastName><ForeName>John R</ForeName><Initials>JR</Initials><AffiliationInfo><Affiliation>Centre for Bioinformatics, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia; Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia; Department of Medicine, John Hunter Hospital and Hunter Medical Research Institute, New Lambton, New South Wales, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Armstrong</LastName><ForeName>Bruce K</ForeName><Initials>BK</Initials><AffiliationInfo><Affiliation>School of Public Health, The University of Sydney and Sax Institute, Sydney, New South Wales, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Clavel</LastName><ForeName>Jacqueline</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>INSERM, U1018, Department of Environmental Epidemiology of Cancers, Villejuif, France; Paris-Sud University, UMR-S1018, Department of Environmental Epidemiology of Cancers, Research Center in Epidemiology and Population Health, Villejuif, France; French National Registry of Childhood Blood Malignancies (RNHE), Villejuif, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Scott</LastName><ForeName>Rodney J</ForeName><Initials>RJ</Initials><AffiliationInfo><Affiliation>Centre for Bioinformatics, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia; School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia; Molecular Genetics, Hunter Area Pathology Service, Newcastle, New South Wales, Australia.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2014</Year><Month>10</Month><Day>13</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>PLoS One</MedlineTA><NlmUniqueID>101285081</NlmUniqueID><ISSNLinking>1932-6203</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C503805">ARID5B protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D004268">DNA-Binding Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C497239">IKZF1 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014157">Transcription Factors</NameOfSubstance></Chemical><Chemical><RegistryNumber>148971-36-2</RegistryNumber><NameOfSubstance UI="D051740">Ikaros Transcription 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Interaction</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D055106" MajorTopicYN="N">Genome-Wide Association Study</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051740" MajorTopicYN="N">Ikaros Transcription Factor</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010290" MajorTopicYN="Y">Parents</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020641" MajorTopicYN="N">Polymorphism, Single Nucleotide</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D054198" MajorTopicYN="N">Precursor Cell Lymphoblastic Leukemia-Lymphoma</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015203" MajorTopicYN="N">Reproducibility of Results</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014157" MajorTopicYN="N">Transcription Factors</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading></MeshHeadingList><OtherID Source="NLM">PMC4195717</OtherID></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2014</Year><Month>06</Month><Day>25</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2014</Year><Month>09</Month><Day>08</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2014</Year><Month>10</Month><Day>14</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2014</Year><Month>10</Month><Day>14</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2015</Year><Month>9</Month><Day>18</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">25310577</ArticleId><ArticleId IdType="doi">10.1371/journal.pone.0110255</ArticleId><ArticleId IdType="pii">PONE-D-14-28304</ArticleId><ArticleId IdType="pmc">PMC4195717</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Australie</li><li>France</li></country></list><tree><country name="Australie"><noRegion><name sortKey="Evans, Tiffany Jane" sort="Evans, Tiffany Jane" uniqKey="Evans T" first="Tiffany-Jane" last="Evans">Tiffany-Jane Evans</name></noRegion><name sortKey="Anderson, Denise" sort="Anderson, Denise" uniqKey="Anderson D" first="Denise" last="Anderson">Denise Anderson</name><name sortKey="Armstrong, Bruce K" sort="Armstrong, Bruce K" uniqKey="Armstrong B" first="Bruce K" last="Armstrong">Bruce K. Armstrong</name><name sortKey="Attia, John R" sort="Attia, John R" uniqKey="Attia J" first="John R" last="Attia">John R. Attia</name><name sortKey="Bowden, Nikola A" sort="Bowden, Nikola A" uniqKey="Bowden N" first="Nikola A" last="Bowden">Nikola A. Bowden</name><name sortKey="Catchpoole, Daniel" sort="Catchpoole, Daniel" uniqKey="Catchpoole D" first="Daniel" last="Catchpoole">Daniel Catchpoole</name><name sortKey="De Klerk, Nicholas H" sort="De Klerk, Nicholas H" uniqKey="De Klerk N" first="Nicholas H" last="De Klerk">Nicholas H. De Klerk</name><name sortKey="Holliday, Elizabeth G" sort="Holliday, Elizabeth G" uniqKey="Holliday E" first="Elizabeth G" last="Holliday">Elizabeth G. Holliday</name><name sortKey="Jamieson, Sarra E" sort="Jamieson, Sarra E" uniqKey="Jamieson S" first="Sarra E" last="Jamieson">Sarra E. Jamieson</name><name sortKey="Lavis, Laura" sort="Lavis, Laura" uniqKey="Lavis L" first="Laura" last="Lavis">Laura Lavis</name><name sortKey="Milne, Elizabeth" sort="Milne, Elizabeth" uniqKey="Milne E" first="Elizabeth" last="Milne">Elizabeth Milne</name><name sortKey="Richardson, Ebony" sort="Richardson, Ebony" uniqKey="Richardson E" first="Ebony" last="Richardson">Ebony Richardson</name><name sortKey="Scott, Rodney J" sort="Scott, Rodney J" uniqKey="Scott R" first="Rodney J" last="Scott">Rodney J. Scott</name><name sortKey="Talseth Palmer, Bente A" sort="Talseth Palmer, Bente A" uniqKey="Talseth Palmer B" first="Bente A" last="Talseth-Palmer">Bente A. Talseth-Palmer</name></country><country name="France"><noRegion><name sortKey="Rudant, Jeremie" sort="Rudant, Jeremie" uniqKey="Rudant J" first="Jérémie" last="Rudant">Jérémie Rudant</name></noRegion><name sortKey="Clavel, Jacqueline" sort="Clavel, Jacqueline" uniqKey="Clavel J" first="Jacqueline" last="Clavel">Jacqueline Clavel</name><name sortKey="Orsi, Laurent" sort="Orsi, Laurent" uniqKey="Orsi L" first="Laurent" last="Orsi">Laurent Orsi</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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