A multi-layer genomic analysis to understand the biological basis of corticosteroid-induced AVN in children with cancer: Toward precision health strategies.

The Problem: Avascular necrosis (AVN) is a serious complication of corticosteroid treatment in some children with cancer, causing bone damage and, in severe cases, requiring surgery. It affects quality of life and places additional burdens on families and healthcare systems. Currently, there are no reliable ways to predict or prevent severe AVN.

Overview of the Research: In a study of 972 children with cancer, I identified four genetic variants strongly linked to corticosteroid-induced AVN. This project will explore how these genetic factors influence AVN risk by validating key predictors in 718 additional patients, pinpointing causal variants, and investigating how these genes affect bone cell responses to corticosteroids.

Anticipated Outcome: Development of a genetic test to identify children at high risk for severe AVN.

Potential Impact: A genetic test for AVN risk would allow doctors to personalize treatment plans for children with cancer. Children identified as high-risk could be monitored more closely or given alternative treatments to prevent AVN from developing in the first place. This would significantly reduce the number of children experiencing this painful and debilitating side effect.