Rudant Jérémie, Orsi Laurent, Bonaventure Audrey, Goujon-Bellec Stéphanie, Baruchel André, Petit Arnaud, Bertrand Yves, Nelken Brigitte, Pasquet Marlène, Michel Gérard, Saumet Laure, Chastagner Pascal, Ducassou Stéphane, Réguerre Yves, Hémon Denis, Clavel Jacqueline
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.
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.
PLoS One. 2015 Mar 25;10(3):e0121348. doi: 10.1371/journal.pone.0121348. eCollection 2015.
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.
全基因组关联研究（GWAS）已确定，参与淋巴细胞分化的两个基因ARID5B和IKZF1中的常见多态性会增加儿童急性淋巴细胞白血病（ALL）的风险。这些发现显著改变了目前ALL病因学的研究领域。在这一新背景下，本探索性研究调查了这些风险等位基因与法国ESCALE研究中普遍存在的非遗传疑似ALL风险因素之间可能的相互作用：孕期母亲使用家用杀虫剂、孕前父亲吸烟，以及一些早期免疫调节的替代指标，即母乳喂养、一岁前常见感染史和出生顺序。分析基于从全国性基于人群的病例对照研究ESCALE中抽取的434例ALL病例和442例欧洲裔对照。通过标准化电话访谈获取非遗传因素的信息。测试了ARID5B中的rs10740055或IKZF1中的rs4132601与每个疑似非遗传因素之间的相互作用，单核苷酸多态性（SNP）编码为次要等位基因计数（趋势变量）。在rs4132601与母亲使用杀虫剂（p = 0.012）、母乳喂养（p = 0.017）和反复早期常见感染（p = 0.0070）之间观察到统计相互作用，等位基因优势比（OR）仅在未接触杀虫剂的儿童（OR = 1.8，95%CI：1.3，2.4）、曾接受母乳喂养的儿童（OR = 1.8，95%CI：1.3，2.5）和曾有反复早期常见感染的儿童（OR = 2.4，95%CI：1.5，3.8）中增加。在接触杀虫剂、未接受母乳喂养且无或很少有常见感染的儿童中，等位基因OR接近1。在仅病例设计中，反复早期常见感染与rs10740055相互作用（p = 0.018）。需要进一步研究来评估这些非遗传因素对风险等位基因效应的修饰观察结果是偶然发现还是反映了真正的潜在机制。
