Four Pharmacogenomic Variants Strongly Linked to Corticosteroid‐Induced Avascular Necrosis in Children with Cancer
Bibliographic record
Abstract
Abstract Corticosteroids are effective anti‐cancer agents for treating hematologic malignancies in children. However, avascular necrosis (AVN) is a common and debilitating adverse effect, leading to bone death and impacting long‐term quality of life. This study aimed to uncover the genetic factors contributing to corticosteroid‐induced AVN in a well‐characterized cohort of pediatric cancer patients. We conducted a genome‐wide association study (GWAS) on 972 patients, including 108 with AVN grade ≥2 and 864 dose‐matched controls. The GWAS of 6.4 million genetic markers identified four significant AVN‐associated loci ( P < 5 × 10 −8 ): WNT7B (OR = 9.2; 95% CI, 3.8‐22.0), POGK (OR = 8.4; 95% CI, 3.6‐19.5), ZNF37A (OR = 6.0; 95% CI, 2.9‐12.5), and a synonymous variant in FAM240C (OR = 5.0; 95% CI, 2.6‐9.5). A multi‐marker predictive model combining single nucleotide polymorphisms (SNPs) and clinical factors showed an area under the ROC curve (AUC) of 78.7%, outperforming SNP‐only (67.8%) and clinical‐only (68.4%) models. The osteogenic processes regulated by WNT7B , part of the Wnt signaling pathway, may contribute to AVN‐related disrupted bone development and repair. Similarly, POGK and ZNF37A , both containing the KRAB domain, are hypothesized to affect osteoblast differentiation and skeletal development in AVN. Developing a predictive model for individual susceptibility to corticosteroid‐induced AVN will enhance the monitoring and management of corticosteroid use in children with cancer.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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; a candidate call from one teacher head, not a consensus.
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".