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Methotrexate Clearance GWAS in Acute Lymphoblastic Leukemia (ALL) Patients
dbGaP
Data Resource:  dbGaP
Point of Contact:  
Mary V. Relling, PharmD,  
Project

About This Dataset
We estimated the plasma clearance of methotrexate from 1279 acute lymphoblastic leukemia (ALL) patients treated on the Children Oncology Group 9904 and 9905 trials. Patients received either a 24-hour infusion of a 1 g/m2 dose or 4-hour infusion of a 2 g/m2 dose). Methotrexate clearance was lower in older children (p=7 x 10-7), females (p=2.7 x 10-4), and patients who received a delayed intensification phase (p=0.0022). In a genome-wide analysis, methotrexate clearance was associated with polymorphisms in the SLCO1B1 gene (p=2.1 x 10-11), which encodes for an organic anion transporter. This replicates findings using different schedules of high-dose methotrexate in ALL patients treated on St. Jude protocols. A combined meta-analysis yields a p-value of 5.7 x 10-19 for the association of methotrexate clearance with SLCO1B1 SNP rs4149056. This dataset includes the dependent variable of methotrexate clearance and all of the SNP data available from arrays.
Core Data Elements
Number of Cases
1,279
Case Sex
Female (621); Male (658)
Case Age At Diagnosis
Pediatric and Young Adult (<40 years) (1,279)
Case Race
Asian (22); Black or African American (58); White (806); Not Reported (393)
Case Ethnicity
Hispanic or Latino (266); Not Hispanic or Latino (1,013)
Case Disease Diagnosis
Acute Lymphoblastic Leukemia (1,279)
Case Tumor Site
Peripheral Blood (1,279)
Additional Data Elements
CLINICAL TRIAL IDENTIFIER
DBGAP STUDY IDENTIFIER
CASE AGE AVERAGE
4.3
CASE AGE MAXIMUM
18
CASE AGE MINIMUM
1
Grant Information
R01CA036401
Pharmacogenomics of Childhood Leukemia ALL
U10CA098413
Children's Oncology Group Statistics and Data Center Grant
U24CA114766
Support for Human Specimen Banking in NCI-Sponsored Clinical Trials-(CGB)
Published In
https://doi.org/10.1101/gr.129668.111;https://doi.org/10.1200/jco.2008.20.4156;https://doi.org/10.1182/blood-2012-08-452839
Charts
Male (658); Female (621)
658Male