title: Associations between genetic variants in folate and drug metabolizing pathways and relapse risk in pediatric acute lymphoid leukemia on CCG-1952.
abstract: Genetic variation in drug detoxification pathways may influence outcomes in pediatric acute lymphoblastic leukemia (ALL). We evaluated relapse risk and 24 variants in 17 genes in 714 patients in CCG-1961. Three TPMT and 1 MTR variant were associated with increased risks of relapse (rs4712327, OR 3.3, 95%CI 1.2-8.6; rs2842947, OR 2.7, 95%CI 1.1-6.8; rs2842935, OR 2.5, 95%CI 1.1-5.0; rs10925235, OR 4.9, 95%CI 1.1-25.1). One variant in SLC19A1 showed a protective effect (rs4819128, OR 0.5, 95%CI 0.3-0.9). Our study provides data that relapse risk in pediatric ALL is associated with germline variations in TPMT, MTR and SLC19A1.
authors.affiliation: Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Marijana
authors.initials: M
authors.lastname: Vujkovic
authors.affiliation: University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Kershenbaum
authors.affiliation: Alfred I. duPont Hospital for Children, Wilmington, DE, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Wray
authors.affiliation: Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: McWilliams
authors.affiliation: University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Cannon
authors.affiliation: Department of Biostatistics, Colleges of Medicine and Public Health and Health Professions, University of Florida, Gainesville, FL, USA.
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Devidas
authors.affiliation: Department of Biostatistics, Colleges of Medicine and Public Health and Health Professions, University of Florida, Gainesville, FL, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Stork
authors.affiliation: Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Aplenc
keywords: Acute lymphoblastic leukemia; Folate pathway; Relapse; SNPs