Journal article

MHC variation and risk of childhood B-cell precursor acute lymphoblastic leukemia

Fay J Hosking, Stephen Leslie, Alexander Dilthey, Loukas Moutsianas, Yufei Wang, Sara E Dobbins, Elli Papaemmanuil, Eamonn Sheridan, Sally E Kinsey, Tracy Lightfoot, Eve Roman, Julie AE Irving, James M Allan, Malcolm Taylor, Mel Greaves, Gilean McVean, Richard S Houlston

BLOOD | AMER SOC HEMATOLOGY | Published : 2011


A role for specific human leukocyte antigen (HLA) variants in the etiology of childhood acute lymphoblastic leukemia (ALL) has been extensively studied over the last 30 years, but no unambiguous association has been identified. To comprehensively study the relationship between genetic variation within the 4.5 Mb major histocompatibility complex genomic region and precursor B-cell (BCP) ALL risk, we analyzed 1075 observed and 8176 imputed single nucleotide polymorphisms and their related haplotypes in 824 BCP-ALL cases and 4737 controls. Using these genotypes we also imputed both common and rare alleles at class I (HLA-A, HLA-B, and HLA-C) and class II (HLA-DRB1, HLA-DQA1, and HLA-DQB1) HLA l..

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University of Melbourne Researchers


Awarded by Medical Research Council

Awarded by Wellcome Trust

Awarded by Cancer Research UK

Funding Acknowledgements

The authors thank Sue Richards and Julie Burrett (Clinical Trials Service Unit, Oxford), Christine Harrison, Lucy Chilton, and Anthony Moorman (Leukemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University), Jill Simpson (University of York), Pamela Thomson and Adiba Hussain (Cancer Immunogenetics, School of Cancer Sciences, University of Manchester) for assistance with data harmonization, Irene Roberts and the Children's Cancer and Leukemia Group Biological Studies Steering Group for access to Medical Research Council ALL Trial samples, all the patients and persons for their participation, and the clinicians, other hospital staff, and study staff who contributed to the blood sample and data collection for this study. This study made use of control genotyping data generated by the Wellcome Trust Case-Control Consortium. The authors acknowledge use of genotype data from the British 1958 Birth Cohort DNA collection, funded by the Medical Research Council (grant G0000934) and the Wellcome Trust (grant 068545/Z/02). A full list of the investigators who contributed to the generation of the data is available from work was supported by Leukaemia & Lymphoma Research (United Kingdom), the Kay Kendall Leukaemia Fund, Cancer Research UK (C1298/A8362 supported by the Bobby Moore Fund), and the Wellcome Trust (award 076113 and 085475).