Abstract 3511: Racial differences in circulating mitochondria-derived peptides may contribute to prostate cancer health disparities

Abstract

Abstract INTRODUCTION AND OBJECTIVES: Our group identified multiple small open reading frames (ORFs) in the mitochondrial genome. These ORFs produce small mitochondrial-derived peptides (MDPs) that are measurable in plasma including humanin, small humanin-like peptide-2 (SHLP2), and mitochondrial open reading frame of the 12S rRNA (MOTSc). Previously we found that higher serum SHLP2 was linked with lower prostate cancer (PC) risk in white men, but no significant association was observed in black men. We tested whether SHLP2 and other MDPs as measured in plasma correlated with PC risk by race in a separate sample of men undergoing prostate biopsy. METHODS: Plasma SHLP2, humanin, and MOTSc were measured by ELISA in 198 men (50/49 white/black cases; 50/49 white/black controls) undergoing prostate biopsy at the Durham Veterans Affair hospital. Logistic and multinomial regression models were used to test the association between each MDP and PC diagnosis and low-grade (grade group 1) and high-grade PC (grade group 2-5). Models were adjusted for age, body mass index, digital rectal examination, and PSA. We tested the interaction between MDPs and race in predicting PC. RESULTS: There was a statistically significant p-interaction between all 3 MDPs and race for predicting PC (all p-interactions values lower than 0.01). Among white men, higher values of all MDPs were significantly associated with lower PC diagnosis (all p-values lower than 0.001). In contrast, in black men, all MDPs were unrelated to PC diagnosis. Similarly, higher expression of all MDPs was associated with decreased risk of both low- and high-grade PC in white men (all p-values lower than 0.005) but none were associated with low- or high-grade in black men. Black controls had lower MOTSc (p-value equal 0.026) and SHLP2 (p-value equal 0.001) values than white controls. CONCLUSIONS: Higher expression of all three MDPs studied (plasma SHLP2, humanin, and MOTSc) were associated with lower PC risk in white men but not in black men. However, in general, black controls had lower MDP levels than white controls. These data support the importance of MDPs and perhaps mitochondrial dysfunction in PC and suggest greater dysfunction in black men (lower MDP levels in controls), which may contribute to excess PC risk in black men, though this requires confirmation in future larger studies. Funding: Supported in part by DODW81XWH, K24CA160653, and U54CA233465. Citation Format: Adela Ramirez-Torres, Allison L. Reagan, Lauren E. Howard, Emily Wiggins, Adriana C. Vidal, Junxiang Wang, Stephen J. Freedland, Pinchas Cohen. Racial differences in circulating mitochondria-derived peptides may contribute to prostate cancer health disparities [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3511.