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Genome-wide homozygosity signatures and childhood acute lymphoblastic leukemia risk

Lookup NU author(s): Professor Julie Irving, Professor James Allan

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Abstract

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)

Publication metadata

Author(s): Hosking FJ, Papaemmanuil E, Sheridan E, Kinsey SE, Lightfoot T, Roman E, Irving JAE, Allan JM, Taylor M, Tomlinson IP, Greaves M, Houlston RS

Publication type: Article

Publication status: Published

Journal: Blood

Year: 2010

Volume: 115

Issue: 22

Pages: 4472-4477

Print publication date: 01/06/2010

ISSN (print): 0006-4971

ISSN (electronic): 1528-0020

Publisher: American Society of Hematology

URL: http://dx.doi.org/10.1182/blood-2009-09-244483

DOI: 10.1182/blood-2009-09-244483

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