Ethnic Disparity of Mitochondrial Peptides and Prostate Cancer Risk
Abstract
Black men have a higher risk of being diagnosed with aggressive prostate cancer and higher prostate cancer mortality compared to white men. Several studies, including our analyses, have also found that black men have lower blood levels of a completely new kind of hormones that we recently discovered; namely, peptides encoded from a part of the cell called the mitochondria, which harbors its own dedicated chromosome. Mitochondrial dysfunction and genetic variation have been associated with many diseases such as diabetes, Alzheimer’s, and cancers such as prostate cancer. Recently, we have discovered novel mitochondrial-derived peptides called humanin and SHLP2, which act as a protective factor against various illnesses. Decreased humanin levels have been implicated in a number of diseases, and we find that African Americans have lower circulating levels of both humanin and SHLP2 compared to Caucasian Americans. Of note, African Americans are also at higher risk for the same diseases that humanin administration has been able to ameliorate -- cardiovascular disease and diabetes -- and our preliminary data suggest the impact of decreased humanin as well as other mitochondrial peptides, particularly SHLP2, among African Americans men may also extend to racial differences in prostate cancer risk and progression. We propose to study the levels of mitochondrial peptides in patients with and without prostate cancer, half of whom will be African Americans and half Caucasians. We will also sequence the mitochondrial DNA of these patients. We will seek to determine if ascertaining mitochondrial-ancestry specific to African-American may help identify at risk individuals and guide therapy. Our proposed study has multiple innovative elements that can explore novel biological pathways; addresses a highly significant health disparity issue in prostate cancer; focuses on mitochondria, which are important in cancer; leverages stored samples from completed, federally funded trials; and utilizes state-of-the-art approaches and exciting new observations in a health disparity population. Our study will be the first to study the racial differences in mitochondrial peptide levels and their effect on prostate cancer. If successful, mitochondrial peptide levels and/or mitochondrial genetic analysis may serve as a diagnostic biomarker of prostate cancer. Furthermore, this study may set the stage for potential mitochondrial-related or nutritional interventions in minority populations, as mitochondrial peptide levels are regulated by interventions that may modify cancer risk (such as diet and exercise).
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710612
Entities
People
- Pinchas Cohen
Organizations
- United States Army
- University of Southern California