Racial disparity exists in various diseases that occur in human. In particular, the incidence and severity of Prostate Cancer is greater in black men than in white men in the United States. There are intrinsic biological differences that account for the differences in disease development and progression, but these differences are under-studied. Socially, cultural beliefs, as well as, inherent biases and systemic racism contribute to disparities in diagnosis, treatment, and prognosis of prostate cancer in black men on the macrolevel. However, at the biomedical and microlevel, an under appreciation or lack of awareness of the significance of ethnic and racial biological differences has resulted in inadequate diversity in bio-specimens and cell-line models in in vitro research.
Precision medicine is a growing field of interest in the treatment of diseases like cancer, where medicine and therapeutic intervention is tailored to the individuals genotype. However, with that, it is necessary to examine how ethnicity and race influence pathogenesis and progression of a disease, as well as, responsiveness to therapeutic intervention. Currently, the majority of biological samples that are collected from patients are collected from those who are classified as white or of European ancestry.
Ethnicity and race have to do with genetic make-up and ancestry. Individuals who share a similar ancestry will share similar genetics, and genetics determine a host of characteristics about an individual including how the cells of their body function. Genes can determine a predisposition for certain diseases and how and when those diseases might present themselves. In men of African ancestry — as this can be seen in black men across the United states, the United Kingdom, the Caribbean, South American, and West Africa; black men have a higher incidence of developing prostate cancer than the remaining population. Black men also tend to experience an earlier onset, greater tumor volume, and poorer prognosis for prostate cancer. Prostate cancer in black men is more aggressive than in their white counterparts, and therefore also has a higher mortality rate. These differences are not completely accounted for by disparities in access to health care and participation in clinical trials; factors that affect early detection and treatment. Prostate cancer cells behave differentially in black men than they do in white men.
Cellular and Genetic Disparity
Studies have found that there are cellular and genetic differences in the tumor biology of prostate cancer cells in black men compared to white men. For instance, it was found that stromal cells called fibroblasts, collected from the area around the tumor of black prostate cancer patients produced pro-inflammatory cytokines and mediators. They also promoted the growth and motility of prostate tumor cells in vitro (cell culture). In vivo, expression of biological markers of fibroblast activation was also elevated in black men with prostate cancer. In comparison to white men, it was determined that prostrate cancer is driven by increased chronic inflammation from the activation of stromal cells.
Additionally, alternate splicing of mRNA (messenger RNA; encodes for protein production) is involved in the development of cancers such as prostate cancer. Differences in mRNA splicing along ethnic or racial lines may be responsible for the disparities seen in prostate cancer in black versus white men. Alternate splicing of mRNA is a process that takes information encoding for one type of protein and alters it to produce isoforms of that protein. So, the other proteins might then have a similar or different shape and function than the original, such that they may have opposing action or act on different cells, to elicit different outcomes. It is thought, that there may be aberrant splicing changes specific to black men that cause changes that promote cancer progression and invasion, leading to more aggressive prostate cancer and increased risk of cancer reoccurrence.
Lack of Availability of African-Amercian Derived Cell-lines
To properly and fully investigate the molecular mechanisms, hormonal, genetic, and epigenetic factors underlying tumor biology and the clinical manifestations of prostate cancer in black men, in vitro cell models of African lineage need to be established and characterized. Currently only 2 virally immortalized prostate cancer cell-lines (derived from normal or healthy prostate epithelial cells from African-American specimens) exist: RC-77T/E and RC165N. Additionally, 2 spontaneously transformed cell-lines derived from the prostate cancer of black men are commercially available for research use: MDA=PCa2a/2b and EOO6AA/EOO6AA-ht. Meanwhile, there are over 12 cell-lines of European ancestry that are used for prostate cancer research. To make matters worse, recently it was discovered through genetic testing that E006AA-ht is actually 91 percent European. Another cell-line, 22Rv1, which was reported in 2017 to be of mixed heritage (approximately equally of African and European origin), was misidentified (not enough genetic markers were included in the panel) and is actually of 99 percent European ancestry according to another larger study published in 2019.
This problem is not only relevant to prostate cancer, but also to colorectal cancer in black men, breast cancer in women, and pregnancy mortality and morbidity in black women. Diversity in the collection of specimens in biomedicine and the establishment and proper characterization of cell-lines of African-American origin is necessary to resolve disparities in therapeutic treatment and the development of precision medicine. Cell-lines of genetic African ancestry are essential for targeting specific genes that drive pathogenesis and disease progression, which may differ between ethnic and racial groups. When the majority of bio-specimens and cell-lines are of European ancestry and there exists a lack of cells from different ethno-racial populations, science is made to be biased against people of non-white ancestry. The National Institute of Health has put forth new guidelines to help change this.
- Stanley E. Hooker Jr., Woods-Burnham L., Bathina M., Lloyd S., Gorjala P., Mitra R., Nonn L. K., Kimbro S., and Rick A. Kittles. Genetic Ancestry Analysis Reveals Misclassification of Commonly Used Cancer Cell Lines. Cancer Epidemiol Biomarkers Prev Vol 28: 6 p 1003-1009; DOI:1158/1055-9965.EPI-18-1132
- Woods-Burnham, L., Basu, A., Cajigas-Du Ross, C. K., Love, A., Yates, C., De Leon, M., Roy, S., & Casiano, C. A. (2017). The 22Rv1 prostate cancer cell line carries mixed genetic ancestry: Implications for prostate cancer health disparities research using pre-clinical models. The Prostate, 77(16), 1601–1608. org/10.1002/pros.23437.
- Gillard M, Javier R, Ji Y, et al. Elevation of Stromal-Derived Mediators of Inflammation Promote Prostate Cancer Progression in African-American Men. Cancer Res. 2018;78(21):6134‐6145. doi:10.1158/0008-5472.CAN-17-3810
- Wang, B. D., Ceniccola, K., Hwang, S., Andrawis, R., Horvath, A., Freedman, J. A., Olender, J., Knapp, S., Ching, T., Garmire, L., Patel, V., Garcia-Blanco, M. A., Patierno, S. R., & Lee, N. H. (2017). Alternative splicing promotes tumour aggressiveness and drug resistance in African American prostate cancer. Nature communications, 8, 15921. https://doi.org/10.1038/ncomms15921
- Koochekpour S, Willard SS, Shourideh M, et al. Establishment and characterization of a highly tumorigenic African American prostate cancer cell line, E006AA-hT. Int J Biol Sci. 2014;10(8):834‐845. Published 2014 Jul 26. doi:10.7150/ijbs.9406
- Paredes, J., Ji, P., Lacomb, J. F., Shroyer, K. R., Martello, L. A., & Williams, J. L. (2018). Establishment of three novel cell lines derived from African American patients with colorectal carcinoma: A unique tool for assessing racial health disparity. International journal of oncology, 53(4), 1516–1528. org/10.3892/ijo.2018.4510
- Robinson AT, Cook MD, Lane-Cordova AD. Making cell culture more physiological: a call for a more comprehensive assessment of racial disparities in endothelial cell culture studies. Am J Physiol Cell Physiol. 2020;318(2):C238‐C241. doi:10.1152/ajpcell.00467.2019
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