Pharmacogenomics of Vincristine‐Induced Peripheral Neuropathy Implicates Pharmacokinetic and Inherited Neuropathy Genes
Bibliographic record
Abstract
Vincristine is an effective chemotherapeutic drug for various cancers, including acute lymphoblastic leukemia ( ALL ). Unfortunately, clinical utility is restricted by dose‐limiting vincristine‐induced peripheral neuropathies ( VIPN ). We sought to determine the association of VIPN with a recently identified risk variant, CEP 72 rs924607, and drug absorption, distribution, metabolism, and excretion ( ADME ) gene variants in pediatric ALL . This was followed by a meta‐analysis of pharmacogenomic data from over 500 patients. CEP 72 rs924607 was significantly associated with VIPN ( P = 0.02; odds ratio ( OR ) = 3.4). ADME analyses identified associations between VIPN and ABCC 1 rs3784867 ( P = 5.34 × 10 −5 ; OR = 4.9), and SLC 5A7 rs1013940 ( P = 9.00 × 10 −4 ; OR = 8.6); genes involved in vincristine transport and inherited neuropathies, respectively. Meta‐analysis identified an association with a variant related to TTPA (rs10504361: P = 6.85 × 10 −4 ; OR = 2.0), a heritable neuropathy‐related gene. This study provides essential corroboratory evidence for CEP 72 rs924607 and highlights the importance of drug transporter and inherited neuropathy genes in VIPN .
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.005 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; both teacher heads agree on what is shown here.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".