Biological sex is an independent risk factor of cancer. Men are three to five times more likely than women to develop bladder cancer even when known risk factors are taken into consideration. Development of sex in mammals is often viewed as a two-step process. The first step is sex determination, of which the XX and XY sex chromosome complements trigger gonad differentiation to form the ovary and testis, respectively. After that, sex hormones secreted by gonads initiate sexually dimorphic differentiation of nongonadal tissues. However, this model has been challenged by recent findings revealing an independent contribution of sex chromosomes to sexual dimorphism. In this chapter, we discuss how the sex chromosomes and sex hormones together cause gender disparities in bladder cancer. We propose a concept of epigenetic sex – epigenetic differences between males and females – and suggest that the sex epigenome is a previously unknown biasing factor contributing to gender disparities in bladder cancer.
Part of the book: Modern Approach to Diagnosis and Treatment of Bladder Cancer