Validation of Gene Expression Differences in Prostate Cancer Tumors of African American Men: Where Do We Go from Here?
Kosj Yamoah, MD, PhD
By Daniel Spratt, MD, University of Michigan
Black men in the United States have the greatest burden of prostate cancer diagnosis and mortality compared to any other race. The root of this disparity is convincingly in part due to social determinants of health, as Black men with prostate cancer are less likely to have insurance, more likely to be of lower socioeconomic and educational status, receive lower rates of guideline concordant care, often delayed in their time to diagnosis and receive less follow-up PSA testing and monitoring after treatment, among likely hundreds more documented disparities rooted in structural racism.
However, a question that remains poorly understood is why Black men are more likely to be diagnosed with prostate cancer given they often have less access to care and, some studies demonstrate, are less willing to seek medical care. Potential answers are rooted in similar social determinants of health, given that obesity and unhealthy diets have been shown to not only increase the likelihood of developing prostate cancer, but also the aggressiveness of harboring a lethal cancer. In contrast, there is data to suggest that African ancestry may carry unique germline genetic risk alleles that increase the potential development of prostate cancer. Regardless of the exact underlying cause, there remains interests in understanding the culmination of these factors on tumor biology.
Prior data from multiple groups have shown that tumors of African American men are enriched for varying immune pathway differences. Kosj Yamoah, MD, PhD, validates this prior data using gene expression data. He presented data in Comparative Genomics to Uncover Distinct Immune-oncologic Pathways in African American Men with Prostate Cancer from retrospective cohorts that had ~400 African American men, as well as a larger group of European American men to compare to. They identified 51 differentially expressed immune specific genes using patients that underwent whole transcriptome microarray testing. They refined this gene list of 35 genes in their validation cohort. Further validation with immunohistochemistry (IHC) will be needed to better understand the true cellular diversity of the microenvironment and the drivers of these potential differences.
How this work will translate to improve Black men’s outcomes with prostate cancer is to be determined. However, regardless of the underlying cause of these immunological differences, there are immediate potential methods to improve outcomes for Black men with prostate cancer by reducing barriers to quality care. I hope scientists continue to investigate the impact of social determinants of health or genetic influences on the immune landscape, and critically, how this can be leveraged to benefit Black men with prostate cancer.
Comparative Genomics to Uncover Distinct Immune-oncologic Pathways in African American Men with Prostate Cancer was presented on Saturday, October 24 in the Science Center, as part of Quick Pitch (QP) session 02.
PubMed Link: https://pubmed.ncbi.nlm.nih.gov/33037017/
Published on: October 25, 2020