Is End-Stage Renal Disease Tumor Suppressive? Dispelling the Myths

TL;DR

This paper reviews evidence suggesting that end-stage renal disease may suppress cancer development and progression, contrary to common beliefs.

Contribution

The study challenges the assumption that end-stage renal disease promotes cancer and highlights its potential tumor-suppressive effects.

Findings

Cancer-specific mortality is generally lower in ESRD patients than in the general population.

ESRD may have anticancer effects through mechanisms like premature aging and enhanced cancer immunity.

Only renal cell and urothelial cancers are driven by ESRD, while others are less aggressive.

Abstract

End-stage renal disease (ESRD) is a life-threatening condition that necessitates renal replacement therapies such as dialysis. ESRD is believed to increase cancer risk and cancer mortality rate; however, data on cancer risk and cancer-specific mortality in patients with ESRD present multiple statistical issues, including sampling errors, bias, and confounding factors, falsely depicting high cancer incidence. Only renal cell and urothelial cancers are driven by ESRD. However, cancer-specific mortality is generally lower in patients with ESRD than in the general population, which corresponds to the fact that cancers arising from ESRD are generally less aggressive and have low metastatic potential. ESRD damages not only normal but also malignant cells in multiple stages of cancer development. This review highlights the potential anticancer effects of ESRD, proposing a reconsideration of the hypothesis that ESRD promotes cancer development and progression.

The prevalence of end-stage renal disease is increasing worldwide. Malignancies accompanying end-stage renal disease are detected in approximately 120 individuals per 10,000 person-years. Most studies have suggested that end-stage renal disease causes carcinogenesis and promotes tumor development; however, this theory remains questionable. Contrary to the theory that end-stage renal disease is predominantly carcinogenic, recent findings have suggested that after controlling for biases and sampling errors, the overall cancer risk in patients with end-stage renal disease might be lower than that in the general population, except for renal and urothelial cancer risks. Additionally, mortality rates associated with most cancers are lower in patients with end-stage renal disease than in the general population. Several biological mechanisms have been proposed to explain the anticancer effects of end-stage renal disease, including premature aging and senescence, enhanced cancer immunity, uremic tumoricidal effects, hormonal and metabolic changes, and dialysis therapy-related factors. Despite common beliefs that end-stage renal disease exacerbates cancer risk, emerging evidence suggests potential tumor-suppressive effects. This review highlights the potential anticancer effects of end-stage renal disease, proposing reconsideration of the hypothesis that end-stage renal disease promotes cancer development and progression.

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