Sex and Gender Differences in Kidney Cancer: Clinical and Experimental Evidence

SIMPLE SUMMARY: Kidney cancer is a frequent malignant tumor that accounts for approximately 5% of all cancer incidences. It affects both males and females, but males are twice as likely to develop kidney cancer than females. Evidence shows that this discrepancy takes root in individual differences, such as genetics or pathologies that affect the patient. It is then reflected in the clinical characteristics of the tumors, as males have larger and more aggressive tumors. Understanding the sex- and gender-based differences in kidney cancer is essential to be able to offer patients individualized medicine that would better cover their needs in terms of prevention, diagnosis and treatment. ABSTRACT: Sex and gender disparities have been reported for different types of non-reproductive cancers. Males are two times more likely to develop kidney cancer than females and have a higher death rate. These differences can be explained by looking at genetics and genomics, as well as other risk factors such as hypertension and obesity, lifestyle, and female sex hormones. Examination of the hormonal signaling pathways bring further insights into sex-related differences. Sex and gender-based disparities can be observed at the diagnostic, histological and treatment levels, leading to significant outcome difference. This review summarizes the current knowledge about sex and gender-related differences in the clinical presentation of patients with kidney cancer and the possible biological mechanisms that could explain these observations. Underlying sex-based differences may contribute to the development of sex-specific prognostic and diagnostic tools and the improvement of personalized therapies.