Examination of HFE associations with childhood leukemia risk and extension to other iron regulatory genes.

Kennedy, Amy E and Kamdar, Kala Y and Lupo, Philip J and Okcu, M Fatih and Scheurer, Michael E and Baum, Marianna K and Dorak, Mehmet Tevfik (2014) Examination of HFE associations with childhood leukemia risk and extension to other iron regulatory genes. Leukemia research, 38 (9). pp. 1055-60. ISSN 1873-5835

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Abstract

Hereditary hemochromatosis (HFE) variants correlating with body iron levels have shown associations with cancer risk, including childhood acute lymphoblastic leukemia (ALL). Using a multi-ethnic sample of cases and controls from Houston, TX, we examined two HFE variants (rs1800562 and rs1799945), one transferrin receptor gene (TFRC) variant (rs3817672) and three additional iron regulatory gene (IRG) variants (SLC11A2 rs422982; TMPRSS6 rs855791 and rs733655) for their associations with childhood ALL. Being positive for either of the HFE variants yielded a modestly elevated odds ratio (OR) for childhood ALL risk in males (1.40, 95% CI=0.83-2.35), which increased to 2.96 (95% CI=1.29-6.80) in the presence of a particular TFRC genotype for rs3817672 (P interaction=0.04). The TFRC genotype also showed an ethnicity-specific association, with increased risk observed in non-Hispanic Whites (OR=2.54, 95% CI=1.05-6.12; P interaction with ethnicity=0.02). The three additional IRG SNPs all showed individual risk associations with childhood ALL in males (OR=1.52-2.60). A polygenic model based on the number of variant alleles in five IRG SNPs revealed a linear increase in risk among males with the increasing number of variants possessed (OR=2.0 per incremental change, 95% CI=1.29-3.12; P=0.002). Our results replicated previous HFE risk associations with childhood ALL in a US population and demonstrated novel associations for IRG SNPs, thereby strengthening the hypothesis that iron excess mediated by genetic variants contributes to childhood ALL risk.

Item Type: Article
Additional Information and Comments: “NOTICE: this is the author’s version of a work that was accepted for publication in Leukemia Research. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Leukemia Research, [VOL 38, ISSUE 9, (2014)] DOI#10.1016/j.leukres.2014.06.016¨
Keywords: Genetic Markers Genetic Predisposition to Disease Childhhood Acute Lymphoblastic Leukemia Genetic Association Studies Iron homeostasis Iron regulatory gene markers
Faculty / Department: Faculty of Science > School of Health Sciences
Depositing User: Mehmet Dorak
Date Deposited: 24 Jun 2016 08:47
Last Modified: 24 Jun 2016 08:47
URI: http://hira.hope.ac.uk/id/eprint/1473

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