Genome-wide homozygosity signatures and childhood acute lymphoblastic leukemia risk.
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.
Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, United Kingdom.
Fay J
FJ
Hosking
Elli
E
Papaemmanuil
Eammon
E
Sheridan
Sally E
SE
Kinsey
Tracy
T
Lightfoot
Eve
E
Roman
Julie A E
JA
Irving
James M
JM
Allan
Malcolm
M
Taylor
Ian P
IP
Tomlinson
Mel
M
Greaves
Richard S
RS
Houlston
D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D005260:Female; D005808:Genes, Recessive; D055106:Genome-Wide Association Study; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D020641:Polymorphism, Single Nucleotide; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D017467:Receptors, Erythropoietin / Q000235:genetics; D012307:Risk Factors; D006113:United Kingdom; D044465:White People / Q000235:genetics
D017467:Receptors, Erythropoietin