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 A E Irving; James M Allan; Malcolm Taylor; Mel Greaves; Gilean McVean; Richard S Houlston

doi:10.1182/blood-2010-08-301598

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 A E Irving
, James M Allan
, Malcolm Taylor
, Mel Greaves
, Gilean McVean
, Richard S Houlston

Health Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

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 loci. Overall, we found no statistically significant association between variants and BCP-ALL risk. We conclude that major histocompatibility complex-defined variation in immune-mediated response is unlikely to be a major risk factor for BCP-ALL.

Original language	English
Pages (from-to)	1633-40
Number of pages	8
Journal	Blood
Volume	117
Issue number	5
DOIs	https://doi.org/10.1182/blood-2010-08-301598
Publication status	Published - 3 Feb 2011

Keywords

Alleles
Case-Control Studies
Child
Child, Preschool
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
Haplotypes
Histocompatibility Antigens Class I
Histocompatibility Antigens Class II
Humans
Male
Polymorphism, Single Nucleotide
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma

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10.1182/blood-2010-08-301598

Cite this

Hosking, F. J., Leslie, S., Dilthey, A., Moutsianas, L., Wang, Y., Dobbins, S. E., Papaemmanuil, E., Sheridan, E., Kinsey, S. E., Lightfoot, T., Roman, E., Irving, J. A. E., Allan, J. M., Taylor, M., Greaves, M., McVean, G., & Houlston, R. S. (2011). MHC variation and risk of childhood B-cell precursor acute lymphoblastic leukemia. Blood, 117(5), 1633-40. https://doi.org/10.1182/blood-2010-08-301598

@article{c5dd2639ec30472f9f5b1485f59ba46b,

title = "MHC variation and risk of childhood B-cell precursor acute lymphoblastic leukemia",

abstract = "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 loci. Overall, we found no statistically significant association between variants and BCP-ALL risk. We conclude that major histocompatibility complex-defined variation in immune-mediated response is unlikely to be a major risk factor for BCP-ALL.",

keywords = "Alleles, Case-Control Studies, Child, Child, Preschool, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Haplotypes, Histocompatibility Antigens Class I, Histocompatibility Antigens Class II, Humans, Male, Polymorphism, Single Nucleotide, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma",

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

year = "2011",

month = feb,

day = "3",

doi = "10.1182/blood-2010-08-301598",

language = "English",

volume = "117",

pages = "1633--40",

journal = "Blood",

issn = "1528-0020",

publisher = "Elsevier B.V.",

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Hosking, FJ, Leslie, S, Dilthey, A, Moutsianas, L, Wang, Y, Dobbins, SE, Papaemmanuil, E, Sheridan, E, Kinsey, SE, Lightfoot, T , Roman, E, Irving, JAE, Allan, JM, Taylor, M, Greaves, M, McVean, G & Houlston, RS 2011, 'MHC variation and risk of childhood B-cell precursor acute lymphoblastic leukemia', Blood, vol. 117, no. 5, pp. 1633-40. https://doi.org/10.1182/blood-2010-08-301598

TY - JOUR

T1 - MHC variation and risk of childhood B-cell precursor acute lymphoblastic leukemia

AU - Hosking, Fay J

AU - Leslie, Stephen

AU - Dilthey, Alexander

AU - Moutsianas, Loukas

AU - Wang, Yufei

AU - Dobbins, Sara E

AU - Papaemmanuil, Elli

AU - Sheridan, Eamonn

AU - Kinsey, Sally E

AU - Lightfoot, Tracy

AU - Roman, Eve

AU - Irving, Julie A E

AU - Allan, James M

AU - Taylor, Malcolm

AU - Greaves, Mel

AU - McVean, Gilean

AU - Houlston, Richard S

PY - 2011/2/3

Y1 - 2011/2/3

N2 - 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 loci. Overall, we found no statistically significant association between variants and BCP-ALL risk. We conclude that major histocompatibility complex-defined variation in immune-mediated response is unlikely to be a major risk factor for BCP-ALL.

AB - 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 loci. Overall, we found no statistically significant association between variants and BCP-ALL risk. We conclude that major histocompatibility complex-defined variation in immune-mediated response is unlikely to be a major risk factor for BCP-ALL.

KW - Alleles

KW - Case-Control Studies

KW - Child

KW - Child, Preschool

KW - Female

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Genotype

KW - Haplotypes

KW - Histocompatibility Antigens Class I

KW - Histocompatibility Antigens Class II

KW - Humans

KW - Male

KW - Polymorphism, Single Nucleotide

KW - Precursor B-Cell Lymphoblastic Leukemia-Lymphoma

UR - https://www.scopus.com/pages/publications/79551615419

U2 - 10.1182/blood-2010-08-301598

DO - 10.1182/blood-2010-08-301598

M3 - Article

C2 - 21059899

SN - 1528-0020

VL - 117

SP - 1633

EP - 1640

JO - Blood

JF - Blood

IS - 5

ER -

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

Abstract

Keywords

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