Confirmation of Childhood Acute Lymphoblastic Leukemia Variants, ARID5B and IKZF1, and Interaction with Parental Environmental Exposures
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...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4195717/ https://www.ncbi.nlm.nih.gov/pubmed/25310577 http://dx.doi.org/10.1371/journal.pone.0110255 |
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author | Evans, Tiffany-Jane Milne, Elizabeth Anderson, Denise de Klerk, Nicholas H. Jamieson, Sarra E. Talseth-Palmer, Bente A. Bowden, Nikola A. Holliday, Elizabeth G. Rudant, Jérémie Orsi, Laurent Richardson, Ebony Lavis, Laura Catchpoole, Daniel Attia, John R. Armstrong, Bruce K. Clavel, Jacqueline Scott, Rodney J. |
author_facet | Evans, Tiffany-Jane Milne, Elizabeth Anderson, Denise de Klerk, Nicholas H. Jamieson, Sarra E. Talseth-Palmer, Bente A. Bowden, Nikola A. Holliday, Elizabeth G. Rudant, Jérémie Orsi, Laurent Richardson, Ebony Lavis, Laura Catchpoole, Daniel Attia, John R. Armstrong, Bruce K. Clavel, Jacqueline Scott, Rodney J. |
author_sort | Evans, Tiffany-Jane |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4195717 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-41957172014-10-15 Confirmation of Childhood Acute Lymphoblastic Leukemia Variants, ARID5B and IKZF1, and Interaction with Parental Environmental Exposures Evans, Tiffany-Jane Milne, Elizabeth Anderson, Denise de Klerk, Nicholas H. Jamieson, Sarra E. Talseth-Palmer, Bente A. Bowden, Nikola A. Holliday, Elizabeth G. Rudant, Jérémie Orsi, Laurent Richardson, Ebony Lavis, Laura Catchpoole, Daniel Attia, John R. Armstrong, Bruce K. Clavel, Jacqueline Scott, Rodney J. PLoS One Research Article 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. Public Library of Science 2014-10-13 /pmc/articles/PMC4195717/ /pubmed/25310577 http://dx.doi.org/10.1371/journal.pone.0110255 Text en © 2014 Evans et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Evans, Tiffany-Jane Milne, Elizabeth Anderson, Denise de Klerk, Nicholas H. Jamieson, Sarra E. Talseth-Palmer, Bente A. Bowden, Nikola A. Holliday, Elizabeth G. Rudant, Jérémie Orsi, Laurent Richardson, Ebony Lavis, Laura Catchpoole, Daniel Attia, John R. Armstrong, Bruce K. Clavel, Jacqueline Scott, Rodney J. Confirmation of Childhood Acute Lymphoblastic Leukemia Variants, ARID5B and IKZF1, and Interaction with Parental Environmental Exposures |
title | Confirmation of Childhood Acute Lymphoblastic Leukemia Variants, ARID5B and IKZF1, and Interaction with Parental Environmental Exposures |
title_full | Confirmation of Childhood Acute Lymphoblastic Leukemia Variants, ARID5B and IKZF1, and Interaction with Parental Environmental Exposures |
title_fullStr | Confirmation of Childhood Acute Lymphoblastic Leukemia Variants, ARID5B and IKZF1, and Interaction with Parental Environmental Exposures |
title_full_unstemmed | Confirmation of Childhood Acute Lymphoblastic Leukemia Variants, ARID5B and IKZF1, and Interaction with Parental Environmental Exposures |
title_short | Confirmation of Childhood Acute Lymphoblastic Leukemia Variants, ARID5B and IKZF1, and Interaction with Parental Environmental Exposures |
title_sort | confirmation of childhood acute lymphoblastic leukemia variants, arid5b and ikzf1, and interaction with parental environmental exposures |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4195717/ https://www.ncbi.nlm.nih.gov/pubmed/25310577 http://dx.doi.org/10.1371/journal.pone.0110255 |
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