The Molecular Profile of Prostate Tumors in African-American Men

Division Of Basic Sciences - Nci

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Abstract

Currently, genomic risk, including genetic ancestry-inferred risk, is considered a nonmodifiable risk factor. Previous studies have shown that West African genetic ancestry is linked to increased prostate cancer risk among Black men, whose risk is higher than that of any other U.S. population group. However, it is unclear whether additional factors play a role in determining this ancestry-related risk. Understanding how genetic ancestry-inferred risk is modifiable by lived experiences, such as the neighborhood environment in which men at increased risk of adverse prostate cancer outcomes reside, is needed. Examining the intersection of genetic ancestry-inferred risk and stress-related exposures (eg, neighborhood deprivation) may allow for multifactorial tailored interventions that account for both genetic and environmental factors. Hence, we investigated whether neighborhood deprivation may modify the association of West African genetic ancestry and prostate cancer risk and mortality. We found that neighborhood environments may modify how West African genetic ancestry is associated with prostate cancer risk (JAMA Network Open; PMID: 39283637). Our data indicate that West African genetic ancestry was a greater risk factor for men residing in neighborhoods with high levels of deprivation than for men living in more affluent neighborhoods. While genetic ancestry-inferred risk has been considered a nonmodifiable risk factor, our findings suggest that genetically inferred risk is a modifiable risk factor, not a determination. Thus, improving the neighborhood environment may alleviate both the prostate cancer burden directly and the risk associated with West African genetic ancestry among men residing in areas with high deprivation. Because viral infection-related host factors are associated with prostate cancer in African American men, as we showed previously (PMID: 30456312), we begun to study the relationship between viral infection history and the disease using a novel technology, termed VirScan (PMID: 32526205). VirScan can detect an infection history related to all human viruses analyzing blood samples. VirScan uses a human virome peptide library displayed by bacteriophages to screen for antivirome antibodies in blood samples. Theoretically, the method should allow for detection of any viral infection in a subject that triggered an immune response in the past. VirScan is fully operational at the LHC and was instrumental to the discovery of a viral exposure signature that identified liver cancer patients prior to a clinical diagnosis (PMID: 32526205). Applying this technology to a cohort of about 4000 men with and without prostate cancer, we are currently examining the viral infection history in men of African descent, and how it relates to disease development and outcome, analyzing men from the NCI-Maryland and NCI-Ghana case-control studies and a prospective cohort from Tobago, West Indies. The virome assessment in all three cohorts has now been completed and the data are being analyzed. Taking advantage of the existing GWAS and immune-oncology marker data for the NCI-Maryland and NCI-Ghana studies and the neighborhood deprivation index for the NCI-Maryland study, we can further integrate these data with the VirScan data to determine whether the viral infection history associates with a distinct immune-oncology marker profile, germline genetic susceptibility markers, or the social environment - further increasing the potential impact of the study. This in an ongoing project with a projected completion in 2026.