Cancer susceptibility of populations with different genetic backgrounds varies significantly for reasons that cannot be solely attributed to socioeconomical and behavioral factors. Human populations of Black African ancestry have a higher risk of aggressive cancer of various types, including keratinocyte-derived squamous cell carcinomas (SCCs).
By focusing on keratinocytes from which squamous cell carcinomas arise, we have found that cells derived from individuals of Black African versus Caucasian ancestries are generally endowed with intrinsically higher oncogenic and self-renewal potential, which are linked with lower mitochondrial OXPHOS activity and higher expression of the HSD17B7 gene, coding for an enzyme involved in sex steroid and cholesterol biosynthesis. Underlying the findings, HSD17B7 plays a general role in positive control of keratinocyte stem cell and oncogenic potential while suppressing mitochondrial activity.
The work points to the importance of integrated genetic and functional studies for probing into different cancer susceptibility among different human populations, from which all can benefit.
HSD17B7 gene in self-renewal and oncogenicity of keratinocytes from Black versus White populations. Xu, Tassone et al., EMBO Mol Med 2021 (http://doi.org/10.15252/emmm.202114133)
- Primary keratinocytes from Black African versus White Caucasian individuals have differential oncogenic and self-renewal potential and differ in levels of mitochondrial OXPHOS activity;
- HSD17B7, coding for a targetable enzyme involved in sex steroid and cholesterol biosynthesis, is a top differentially expressed gene in keratinocytes and Head/Neck SCCs from individuals of the two ancestries;
- HSD17B7 activity is a key determinant of keratinocyte self renewal and oncogenic potential and mitochondrial OXPHOS activity.