Candidate gene association analysis of acute lymphoblastic leukemia identifies new susceptibility locus at 11p15 (LMO1)

Joke Beuten; Jonathan A L Gelfond; Duangjai Piwkham; Brad H. Pollock; Naomi J. Winick; Anderson B. Collier; Gail E. Tomlinson

doi:10.1093/carcin/bgr091

Candidate gene association analysis of acute lymphoblastic leukemia identifies new susceptibility locus at 11p15 (LMO1)

Joke Beuten, Jonathan A L Gelfond, Duangjai Piwkham, Brad H. Pollock, Naomi J. Winick, Anderson B. Collier, Gail E. Tomlinson

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16 Scopus citations

Abstract

To determine the contribution of susceptibility loci in explaining the genetic basis of acute lymphoblastic leukemia (ALL), we genotyped 29 high-potential candidate genes with 672 tagged single-nucleotide polymorphisms (SNPs) in a sample (163 cases and 251 healthy controls) of Caucasian children. Fifty SNPs in 15 genes were significantly associated with ALL risk at the P < 0.05 level. After correction for multiple testing, rs442264 within the LIM domain only 1 (LMO1) gene at 11p15 remained significant [odds ratio (OR) = 1.90, P= 3× 10^-5]. In addition, a major haplotype within LMO1 comprising 14 SNPs with individual risk associations was found to significantly increase ALL risk (OR 5 1.79, P 5 0.0006). A stratified analysis on subtype indicated that risk associations of LMO1 variants are significant in children with precursor B-cell leukemia. These data show that genetic variants within LMO1 are associated with ALL and identify this gene as a strong candidate for precursor B-cell leukemogenesis.

Original language	English (US)
Pages (from-to)	1349-1353
Number of pages	5
Journal	Carcinogenesis
Volume	32
Issue number	9
DOIs	https://doi.org/10.1093/carcin/bgr091
State	Published - Sep 2011

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Cancer Research

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title = "Candidate gene association analysis of acute lymphoblastic leukemia identifies new susceptibility locus at 11p15 (LMO1)",

abstract = "To determine the contribution of susceptibility loci in explaining the genetic basis of acute lymphoblastic leukemia (ALL), we genotyped 29 high-potential candidate genes with 672 tagged single-nucleotide polymorphisms (SNPs) in a sample (163 cases and 251 healthy controls) of Caucasian children. Fifty SNPs in 15 genes were significantly associated with ALL risk at the P < 0.05 level. After correction for multiple testing, rs442264 within the LIM domain only 1 (LMO1) gene at 11p15 remained significant [odds ratio (OR) = 1.90, P= 3× 10-5]. In addition, a major haplotype within LMO1 comprising 14 SNPs with individual risk associations was found to significantly increase ALL risk (OR 5 1.79, P 5 0.0006). A stratified analysis on subtype indicated that risk associations of LMO1 variants are significant in children with precursor B-cell leukemia. These data show that genetic variants within LMO1 are associated with ALL and identify this gene as a strong candidate for precursor B-cell leukemogenesis.",

author = "Joke Beuten and Gelfond, {Jonathan A L} and Duangjai Piwkham and Pollock, {Brad H.} and Winick, {Naomi J.} and Collier, {Anderson B.} and Tomlinson, {Gail E.}",

note = "Funding Information: Hyundai Hope on Wheels [44096 to J.B. and G.E.T.]; the Texas Higher Education Coordinating Board [010019-0105-2001 to G.E.T.]; the Children{\textquoteright}s Cancer Fund Dallas to G.E.T.; the Greehey Family Foundation to G.E.T. and the Commission on Higher Education Scholarship, Thailand, to D.P.",

year = "2011",

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doi = "10.1093/carcin/bgr091",

language = "English (US)",

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AU - Pollock, Brad H.

AU - Winick, Naomi J.

AU - Collier, Anderson B.

AU - Tomlinson, Gail E.

N1 - Funding Information: Hyundai Hope on Wheels [44096 to J.B. and G.E.T.]; the Texas Higher Education Coordinating Board [010019-0105-2001 to G.E.T.]; the Children’s Cancer Fund Dallas to G.E.T.; the Greehey Family Foundation to G.E.T. and the Commission on Higher Education Scholarship, Thailand, to D.P.

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N2 - To determine the contribution of susceptibility loci in explaining the genetic basis of acute lymphoblastic leukemia (ALL), we genotyped 29 high-potential candidate genes with 672 tagged single-nucleotide polymorphisms (SNPs) in a sample (163 cases and 251 healthy controls) of Caucasian children. Fifty SNPs in 15 genes were significantly associated with ALL risk at the P < 0.05 level. After correction for multiple testing, rs442264 within the LIM domain only 1 (LMO1) gene at 11p15 remained significant [odds ratio (OR) = 1.90, P= 3× 10-5]. In addition, a major haplotype within LMO1 comprising 14 SNPs with individual risk associations was found to significantly increase ALL risk (OR 5 1.79, P 5 0.0006). A stratified analysis on subtype indicated that risk associations of LMO1 variants are significant in children with precursor B-cell leukemia. These data show that genetic variants within LMO1 are associated with ALL and identify this gene as a strong candidate for precursor B-cell leukemogenesis.

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Candidate gene association analysis of acute lymphoblastic leukemia identifies new susceptibility locus at 11p15 (LMO1)

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