Editing Kidney Cancer: Epidemiology and Pathogenesis (section)

====== <span style="color:#ff0000">Von Hippel-Lindau Disease</span> ======
*Incidence 1:30,000-1:40,000
*'''<span style="color:#ff0000">RCC develops in 35-70% of VHL patients</span> and is''' '''distinctive for early age (median 40) of onset and bilateral and multifocal involvement'''
*'''<span style="color:#ff0000">Mutation: VHL</span>'''
**'''VHL is a tumor suppressor gene,''' for both familial and sporadic ccRCC, at '''chromosome 3'''p25-26
***'''<span style="color:#ff0000">VHL mutation is most common genetic mutation in sporadic RCC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3483538/]</span>'''
**Under normal conditions, the '''<span style="color:#ff0000">VHL complex targets hypoxia-inducible factors (HIF) for degradation</span>''', keeping levels of HIF low. HIF regulates response to hypoxia, starvation, and other stresses
**'''<span style="color:#ff0000">In the absence of VHL, HIF accumulates and leads to overexpression of vascular endothelial growth factor (VEGF), the primary angiogenic growth factor in RCC''', contributing to the neovascularity associated with ccRCC.
***Production of erythropoietin (EPO) is closely associated with circulating oxygen levels. During conditions of hypoxia, hypoxia-inducible factor-1-alpha (HIF-1-a) is upregulated increasing EPO transcription. HIF-1-a is then rapidly degraded by proteases upon restoration of normal oxygen tension.
*'''<span style="color:#ff0000">Pheochromocytoma manifestations of VHL are restricted to certain families (type 2 VHL)</span>'''
*'''Patients suspected of having VHL, or the appropriate relatives of those with documented disease, should strongly consider genetic evaluation.'''
**Patients with germline mutations of the VHL gene can be offered screening to identify major manifestations of VHL at a pre-symptomatic phase
*'''<span style="color:#ff0000">RCC is most common cause of death in VHL patients</span>'''