Human populations of Black African ancestry have a relatively high risk of aggressive cancer types, including keratinocyte-derived squamous cell carcinomas (SCCs). We show that primary keratinocytes (HKCs) from Black African (Black) versus White Caucasian (White) individuals have on average higher oncogenic and self-renewal potential, which are inversely related to mitochondrial electron transfer chain activity and ATP and ROS production. HSD17B7 is the top-ranked differentially expressed gene in HKCs and Head/Neck SCCs from individuals of Black African versus Caucasian ancestries, with several ancestry-specific eQTLs linked to its expression. Mirroring the differences between Black and White HKCs, modulation of the gene, coding for an enzyme involved in sex steroid and cholesterol biosynthesis, determines HKC and SCC cell proliferation and oncogenicity as well as mitochondrial OXPHOS activity. Overall, the findings point to a targetable determinant of cancer susceptibility among different human populations, amenable to prevention and management of the disease.

中文翻译：

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HSD17B7 基因在黑人与白人群体角质形成细胞自我更新和致癌性中的作用

非洲黑人血统的人群患侵袭性癌症类型的风险相对较高，包括角质形成细胞源性鳞状细胞癌 (SCC)。我们发现，非洲黑人（黑人）与白种人（白人）的初级角质形成细胞（HKC）平均具有更高的致癌和自我更新潜力，这与线粒体电子传递链活性以及 ATP 和 ROS 产生呈负相关。HSD17B7是非洲黑人与白种人血统个体的 HKC 和头颈 SCC 中排名最高的差异表达基因，多个血统特异性 eQTL 与其表达相关。反映黑人和白人 HKC 之间的差异，对编码参与性类固醇和胆固醇生物合成的酶的基因进行调节，决定 HKC 和 SCC 细胞增殖和致癌性以及线粒体 OXPHOS 活性。总体而言，研究结果指出了不同人群中癌症易感性的一个有针对性的决定因素，适合预防和管理该疾病。