MHC variation and risk of childhood B-cell precursor acute lymphoblastic leukemia.
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.
Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, United Kingdom.
Fay J
FJ
Hosking
Stephen
S
Leslie
Alexander
A
Dilthey
Loukas
L
Moutsianas
Yufei
Y
Wang
Sara E
SE
Dobbins
Elli
E
Papaemmanuil
Eamonn
E
Sheridan
Sally E
SE
Kinsey
Tracy
T
Lightfoot
Eve
E
Roman
Julie A E
JA
Irving
James M
JM
Allan
Malcolm
M
Taylor
Mel
M
Greaves
Gilean
G
McVean
Richard S
RS
Houlston
D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II