Genome-wide homozygosity signatures and childhood acute lymphoblastic leukemia risk

被引：32

作者：

Hosking, Fay J. ^{[1
]}

Papaemmanuil, Elli ^{[1
]}

Sheridan, Eammon ^{[2
]}

Kinsey, Sally E. ^{[3
]}

Lightfoot, Tracy ^{[4
]}

Roman, Eve ^{[4
]}

Irving, Julie A. E. ^{[5
]}

Allan, James M. ^{[5
]}

Taylor, Malcolm ^{[6
]}

Tomlinson, Ian P. ^{[7
]}

Greaves, Mel ^{[8
]}

Houlston, Richard S. ^{[1
]}

机构：

[1] Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England

[2] St James Univ Hosp, Yorkshire Reg Genet Serv, Leeds LS9 7TF, W Yorkshire, England

[3] St James Univ Hosp, Dept Paediat & Adolescent Oncol & Haematol, Leeds LS9 7TF, W Yorkshire, England

[4] Univ York, Epidemiol & Genet Unit, Dept Hlth Sci, York YO10 5DD, N Yorkshire, England

[5] Newcastle Univ, No Inst Canc Res, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England

[6] Univ Manchester, St Marys Hosp, Canc Immunogenet Grp, Sch Canc Sci, Manchester M13 0JH, Lancs, England

[7] Wellcome Trust Ctr Human Genet, Oxford, England

[8] Inst Canc Res, Sect Haematooncol, Sutton SM2 5NG, Surrey, England

来源：

BLOOD | 2010年 / 115卷 / 22期

关键词：

COLORECTAL-CANCER; CONSANGUINITY; POPULATION; LOCI; SUSCEPTIBILITY; INDIVIDUALS; ASSOCIATION; GENETICS; DISEASE;

D O I：

10.1182/blood-2009-09-244483

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Recent studies have reported that regions of homozygosity (ROH) in the genome are detectable in outbred populations and can be associated with an increased risk of malignancy. To examine whether homozygosity is associated with an increased risk of developing childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL), we analyzed 824 ALL cases and 2398 controls genotyped for 292 200 tagging SNPs. Across the genome, cumulative distribution of ROH was not significantly different between cases and controls. Four common ROH at 10p11.2-10q11.21, 1p31.1, 19p13.2-3, and 20q11.1-23 were, however, associated with ALL risk at P less than .01 (including 1 ROH to which the erythropoietin receptor [ EPOR] gene maps, P = .005) but were nonsignificant after adjusting for multiple testing. Our findings make it unlikely that levels of measured homozygosity, caused by autozygosity, uniparental isodisomy, or hemizygosity, play a major role in defining BCP-ALL risk in predominantly outbred populations. (Blood. 2010; 115(22): 4472-4477)

引用

页码：4472 / 4477

页数：6

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