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Abstract: TH-OR070

Clonal Hematopoiesis and AKI in Estrogen-Dependent Cancers

Session Information

Category: Onconephrology

  • 1700 Onconephrology

Authors

  • Won, Alice H., Memorial Sloan Kettering Cancer Center, New York, New York, United States
  • Ruthen, Neil, Memorial Sloan Kettering Cancer Center, New York, New York, United States
  • Tan, Hui Zhuan, Singapore General Hospital, Singapore, Singapore
  • Reznik, Ed, Memorial Sloan Kettering Cancer Center, New York, New York, United States
  • Jaimes, Edgar A., Memorial Sloan Kettering Cancer Center, New York, New York, United States
Background

Clonal hematopoiesis of indeterminate potential (CHIP) has been linked to a higher risk for acute kidney injury (AKI) in the general population. However, whether CHIP confers increased risk for AKI independent of known cancer-associated risk factors remains unknown

Methods

From a single institutional database, we identified 24,811 patients with solid tumors, with longitudinal serum creatinine ([sCr]) values, targeted sequencing of paired tumor and blood samples (MSKCC-IMPACT), and well-documented treatments. We performed competing risk analyses over Cox proportional hazards models to test for the association of CHIP and time to AKI from the date of blood sample collection, adjusting for other risk factors

Results

We report that mutations in PPM1D and other DNA damage response (DDR) genes are significantly associated with decreased time to AKI in breast, endometrial, ovarian, and non-small cell lung cancers. As the estrogen receptor is a transcriptional regulator of DDR genes, we further demonstrate that receipt of estrogen receptor antagonists and selective estrogen receptor modulators is associated with decreased risk of AKI

Conclusion

Our study reveals specific CHIP mutations as prognostic markers for AKI in the context of specific tumor-associated physiologies

Digital Object Identifier (DOI)