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

被引:18
作者
Hosking, Fay J. [1 ]
Leslie, Stephen [2 ]
Dilthey, Alexander [2 ]
Moutsianas, Loukas [2 ]
Wang, Yufei [1 ]
Dobbins, Sara E. [1 ]
Papaemmanuil, Elli [1 ]
Sheridan, Eamonn [3 ]
Kinsey, Sally E. [4 ]
Lightfoot, Tracy [5 ]
Roman, Eve [5 ]
Irving, Julie A. E. [6 ]
Allan, James M. [6 ]
Taylor, Malcolm [7 ]
Greaves, Mel [8 ]
McVean, Gilean [2 ]
Houlston, Richard S. [1 ]
机构
[1] Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England
[2] Univ Oxford, Dept Stat, Oxford OX1 3TG, England
[3] St James Univ Hosp, Yorkshire Reg Genet Serv, Leeds LS9 7TF, W Yorkshire, England
[4] St James Univ Hosp, Dept Paediat & Adolescent Oncol & Haematol, Leeds LS9 7TF, W Yorkshire, England
[5] Univ York, Dept Hlth Sci, Epidemiol & Genet Unit, York YO10 5DD, N Yorkshire, England
[6] Newcastle Univ, No Inst Canc Res, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
[7] Univ Manchester, St Marys Hosp, Sch Canc & Enabling Sci, Canc Immunogenet Grp, Manchester M13 0JH, Lancs, England
[8] Inst Canc Res, Sect Haematooncol, Sutton SM2 5NG, Surrey, England
基金
英国惠康基金; 英国医学研究理事会;
关键词
HLA ALLELES; SUSCEPTIBILITY; ASSOCIATION; HLA-DPB1-ASTERISK-0201; ETIOLOGY; DISEASE;
D O I
10.1182/blood-2010-08-301598
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 Mbmajor 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 bothcommonand 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-ALLrisk. We conclude that major histocompatibility complex-defined variation in immune-mediated response is unlikely to be a major risk factor for BCP-ALL. (Blood. 2011; 117(5): 1633-1640)
引用
收藏
页码:1633 / 1640
页数:8
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