Precursor B-Cell Lymphoblastic Leukemia-Lymphoma study with SNP Genotypes (Array) data on dbGaP (1,267 participants)

phs000637 — Methotrexate Clearance GWAS

<p>We estimated the plasma clearance of methotrexate from 1279 acute lymphoblastic leukemia (ALL) patients treated on the Children Oncology Group 9904 and 9905 trials (<a href="http://clinicaltrials.gov/show/NCT00005585">http://clinicaltrials.gov/show/NCT00005585</a> and <a href="http://clinicaltrials.gov/show/NCT00005596)">http://clinicaltrials.gov/show/NCT00005596</a>). 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 (Trevino et al, PMID 19901119 and Ramsey et al, PMID 23233662). This data set includes the dependent variable of methotrexate clearance and all of the SNP data available from arrays.</p>