ERR1 and PGC1α associated mitochondrial alterations correlate with pan-cancer disparity in African Americans.

BACKGROUND. African American patients have higher cancer mortality rates and shorter survival times compared with European American patients. Despite a significant focus on socioeconomic factors, recent findings strongly argue the existence of biological factors driving this disparity. Most of these factors have been described in a cancer-type specific context rather than a pan-cancer setting. METHODS. A novel in silico approach based on Gene Set Enrichment Analysis (GSEA) coupled to transcription factor enrichment was carried out to identify common biological drivers of pan-cancer racial disparity using The Cancer Genome Atlas data set. Mitochondrial content in patient tissues was examined using a multi-cancer tissue microarray approach (TMA). RESULTS. Mitochondrial oxidative phosphorylation was uniquely enriched in tumors from African American patients compared with tumors of various cancer types from European American patients. Tumors from African American patients also showed strong enrichment for the ERR1-PGC1a-mediated transcriptional program, which has been implicated in mitochondrial biogenesis. TMA analysis revealed that cancers from African American patients harbor significantly more mitochondria compared with the same cancers from European American patients. CONCLUSION. These findings highlight changes in mitochondria as a common distinguishing feature among tumors from African American versus European American patients in a pan-cancer setting, and provide the rationale for the repurposing of mitochondrial inhibitors to treat cancers from African American patients.