title: ARID5B, IKZF1 and non-genetic factors in the etiology of childhood acute lymphoblastic leukemia: the ESCALE study.
abstract: Genome-wide association studies (GWAS) have identified that frequent polymorphisms in ARID5B and IKZF1, two genes involved in lymphoid differentiation, increase the risk of childhood acute lymphoblastic leukemia (ALL). These findings markedly modified the current field of research on the etiology of ALL. In this new context, the present exploratory study investigated the possible interactions between these at-risk alleles and the non-genetic suspected ALL risk factors that were of sufficient prevalence in the French ESCALE study: maternal use of home insecticides during pregnancy, preconception paternal smoking, and some proxies for early immune modulation, i.e. breastfeeding, history of common infections before age one year, and birth order. The analyses were based on 434 ALL cases and 442 controls of European origin, drawn from the nationwide population-based case-control study ESCALE. Information on non-genetic factors was obtained by standardized telephone interview. Interactions between rs10740055 in ARID5B or rs4132601 in IKZF1 and each of the suspected non-genetic factors were tested, with the SNPs coded as counts of minor alleles (trend variable). Statistical interactions were observed between rs4132601 and maternal insecticide use (p = 0.012), breastfeeding p = 0.017) and repeated early common infections (p = 0.0070), with allelic odds ratios (OR) which were only increased among the children not exposed to insecticides (OR = 1.8, 95%CI: 1.3, 2.4), those who had been breastfed (OR = 1.8, 95%CI: 1.3, 2.5) and those who had had repeated early common infections (OR = 2.4, 95%CI: 1.5, 3.8). The allelic ORs were close to one among children exposed to insecticides, who had not been breastfed and who had had no or few common infections. Repeated early common infections interacted with rs10740055 (p = 0.018) in the case-only design. Further studies are needed to evaluate whether these observations of a modification of the effect of the at-risk alleles by non-genetic factors are chance findings or reflect true underlying mechanisms.
authors: Institut national de la santé et de la recherche médicale (INSERM) U1153, Epidemiology and Biostatistics Sorbonne Paris Cité Center (CRESS), Epidemiology of childhood and adolescent cancers team (EPICEA), Villejuif, France; Paris-Descartes University, UMRS-1153, Epidemiology and Biostatistics Sorbonne Paris Cité Center (CRESS), Paris, France; French National Registry of Childhood Hematopoietic Malignancies (RNHE), Villejuif, France.
authors: Jérémie
authors: J
authors: Rudant
authors: Institut national de la santé et de la recherche médicale (INSERM) U1153, Epidemiology and Biostatistics Sorbonne Paris Cité Center (CRESS), Epidemiology of childhood and adolescent cancers team (EPICEA), Villejuif, France; Paris-Descartes University, UMRS-1153, Epidemiology and Biostatistics Sorbonne Paris Cité Center (CRESS), Paris, France.
authors: Laurent
authors: L
authors: Orsi
authors: Institut national de la santé et de la recherche médicale (INSERM) U1153, Epidemiology and Biostatistics Sorbonne Paris Cité Center (CRESS), Epidemiology of childhood and adolescent cancers team (EPICEA), Villejuif, France; Paris-Descartes University, UMRS-1153, Epidemiology and Biostatistics Sorbonne Paris Cité Center (CRESS), Paris, France.
authors: Audrey
authors: A
authors: Bonaventure
authors: Institut national de la santé et de la recherche médicale (INSERM) U1153, Epidemiology and Biostatistics Sorbonne Paris Cité Center (CRESS), Epidemiology of childhood and adolescent cancers team (EPICEA), Villejuif, France; Paris-Descartes University, UMRS-1153, Epidemiology and Biostatistics Sorbonne Paris Cité Center (CRESS), Paris, France; French National Registry of Childhood Hematopoietic Malignancies (RNHE), Villejuif, France.
authors: Stéphanie
authors: S
authors: Goujon-Bellec
authors: Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Paris, France; Université Paris Diderot-Paris 7, Sorbonne Paris Cité, Paris, France.
authors: André
authors: A
authors: Baruchel
authors: Assistance Publique-Hôpitaux de Paris, HUEP, Hôpital Trousseau, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR S_938, Paris, France.
authors: Arnaud
authors: A
authors: Petit
authors: Institut d'Hémato-Oncologie Pédiatrique, Lyon, France; Université Claude Bernard Lyon 1, Lyon, France.
authors: Yves
authors: Y
authors: Bertrand
authors: Pôle Enfant, CHRU, Lille, France; Université Lille Nord de France, Lille, France.
authors: Brigitte
authors: B
authors: Nelken
authors: Hématologie pédiatrique, CHU Toulouse, INSERM U1037, Equipe 16, CRCT, Oncopôle, Toulouse, France.
authors: Marlène
authors: M
authors: Pasquet
authors: Department of Pediatric Hematology and Oncology, Timone Enfants Hospital, Marseille, France; Aix-Marseille University, Marseille, France.
authors: Gérard
authors: G
authors: Michel
authors: Hôpital Arnaud de Villeneuve, Montpellier, France.
authors: Laure
authors: L
authors: Saumet
authors: Hôpital d'enfants, CHU de Nancy, Vandoeuvre, France.
authors: Pascal
authors: P
authors: Chastagner
authors: Hôpital Pellegrin Tripode, Bordeaux, France.
authors: Stéphane
authors: S
authors: Ducassou
authors: CHU Félix Guyon, Saint Denis de La Réunion, France.
authors: Yves
authors: Y
authors: Réguerre
authors: Institut national de la santé et de la recherche médicale (INSERM) U1153, Epidemiology and Biostatistics Sorbonne Paris Cité Center (CRESS), Epidemiology of childhood and adolescent cancers team (EPICEA), Villejuif, France; Paris-Descartes University, UMRS-1153, Epidemiology and Biostatistics Sorbonne Paris Cité Center (CRESS), Paris, France.
authors: Denis
authors: D
authors: Hémon
authors: Institut national de la santé et de la recherche médicale (INSERM) U1153, Epidemiology and Biostatistics Sorbonne Paris Cité Center (CRESS), Epidemiology of childhood and adolescent cancers team (EPICEA), Villejuif, France; Paris-Descartes University, UMRS-1153, Epidemiology and Biostatistics Sorbonne Paris Cité Center (CRESS), Paris, France; French National Registry of Childhood Hematopoietic Malignancies (RNHE), Villejuif, France.
authors: Jacqueline
authors: J
authors: Clavel
mesh_terms: D000293:Adolescent; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000209:etiology* / Q000235:genetics*; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: C503805:ARID5B protein, human; D004268:DNA-Binding Proteins; C497239:IKZF1 protein, human; D014157:Transcription Factors; D051740:Ikaros Transcription Factor