Associations between genetic variants in folate and drug metabolizing pathways and relapse risk in pediatric acute lymphoid leukemia on CCG-1952

Marijana Vujkovic; Aaron Kershenbaum; Lisa Wray; Thomas McWilliams; Shannon Cannon; Meenakshi Devidas; Linda Stork; Richard Aplenc

doi:10.1016/j.lrr.2015.05.005

Associations between genetic variants in folate and drug metabolizing pathways and relapse risk in pediatric acute lymphoid leukemia on CCG-1952

Leuk Res Rep. 2015 Jul 21;4(2):47-50. doi: 10.1016/j.lrr.2015.05.005. eCollection 2015.

Authors

Marijana Vujkovic¹, Aaron Kershenbaum², Lisa Wray³, Thomas McWilliams¹, Shannon Cannon⁴, Meenakshi Devidas⁵, Linda Stork⁵, Richard Aplenc¹

Affiliations

¹ Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
² University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
³ Alfred I. duPont Hospital for Children, Wilmington, DE, USA.
⁴ University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
⁵ Department of Biostatistics, Colleges of Medicine and Public Health and Health Professions, University of Florida, Gainesville, FL, USA.

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.

Keywords: Acute lymphoblastic leukemia; Folate pathway; Relapse; SNPs.