Estimating Mosaic Loss of the Y Chromosome in Male Bladder Cancer Participants Using "All of Us" Data.

Mosaic loss of the Y chromosome (mLOY) is a biologically important alteration in male bladder cancer, associated with tumor aggressiveness and immune evasion. However, scalable methods for estimating mLOY using data from "All of Us" Research Program (AoU) remain limited. This study aimed to develop an analytical pipeline to estimate mLOY using a pliot sample of male bladder cancer subjects (mean age [SD] = 67.80 [10.60] years) from the AoU. We conducted sensitivity analyses to evaluate robustness and accuracy of the pipeline. Estimated mLOY values were further used to assess associations with smoking status. The pipeline was stable and yielded accurate results (Pearson's correlation coefficient = 0.98, p = 5.21 × 10-73). Ever smokers had significantly higher odds of mLOY compared with never smokers (odds ratio = 1.56, p = 0.023). This analytical pipeline provides a robust and scalable framework for mLOY estimation and enables future large-scale analyses using AoU data.