Small open reading frames (sORF) in the mitochondrial genome generate quantifiable mitochondrial-derived peptides (MDPs), such as humanin, SHLP2, and MOTS-c. Prior research on males who had prostate biopsies revealed that greater blood SHLP2 levels were associated with a decreased incidence of prostate cancer (PC) in European American men (EAM), but no relationships were identified in African American men (AAM). For a study, researchers investigated the relationship between PC risk by race and SHLP2, humanin, and MOTS-c in various individuals having a prostate biopsy.

A total of 198 males who were undergoing biopsy (50/49 EAM/AAM cases; 50/49 EAM/AAM controls) had their plasma SHLP2, humanin, and MOTS-c levels tested. Associations between each MDP and PC diagnosis, low-grade (grade group, GG1) and high-grade (GG2-5), were examined using logistic and multinomial regression models. Age, body mass index, digital rectal examination, and prostate specific antigen (PSA) model adjustments. They investigated the effects of race and MDPs.

Humanin was equal between races among controls (P=0.60), whereas SHLP2 (P=0.007) and MOTS-c (P=0.026) were lower in AAM controls compared to EAM controls. Higher MDP values were linked to decreased PC risk in EAM (all P≤0.001), whereas there were no relationships in AAM (all P-interactions≤0.01). In EAM, increased MDP expression was linked to a lower risk of both low- and high-grade PC (P≤ 0.005) but not to any relationships in AAM.

In EAM but not AAM, higher MDP levels were linked to decreased PC risk. MDP levels were generally lower in AAM controls. The findings corroborated MDPs and mitochondrial dysfunction in PC, indicating that more AAM dysfunction may increase the likelihood of developing PC. The findings needed to be confirmed by bigger, future investigations.