Molecular differences in renal cell carcinoma between males and females

Purpose: The disparity in renal cell carcinoma (RCC) risk and treatment outcome between males and females is well documented, but the underlying molecular mechanisms remain poorly elucidated.

Methods: We performed a narrative review synthesizing contemporary evidence on sex-specific molecular differences in healthy kidney tissue and RCC.

Results: In healthy kidney tissue, gene expression differs significantly between males and females, including autosomal and sex-chromosome-linked genes. The differences are most prominent for sex-chromosome-linked genes and attributable to Escape from X chromosome-linked inactivation and Y chromosome loss. The frequency distribution of RCC histologies varies between the sexes, particularly for papillary, chromophobe, and translocation RCC. In clear-cell and papillary RCC, sex-specific gene expressions are pronounced, and some of these genes are amenable to pharmacotherapy. However, for many, the impact on tumorigenesis remains poorly understood. In clear-cell RCC, molecular subtypes and gene expression pathways have distinct sex-specific trends, which also apply to the expression of genes implicated in tumor progression.

Conclusion: Current evidence suggests meaningful genomic differences between male and female RCC, highlighting the need for sex-specific RCC research and personalized sex-specific treatment approaches.