Genetic Contributions to Prostate Cancer Disparities in Men of West African Descent

Abstract

Prostate cancer (PCa) is the second most frequently diagnosed malignancy and the second leading cause of death in men worldwide, after adjusting for age. According to the International Agency for Research on Cancer, continents such as North America and Europe report higher incidence of PCa; however, mortality rates are highest among men of African ancestry in the western, southern, and central regions of Africa and the Caribbean. The American Cancer Society reports, African Americans (AAs), in the United States, have a 1.7 increased incidence and 2.4 times higher mortality rate, compared to European American’s (EAs). Hence, early population history in west Africa and the subsequent African Diaspora may play an important role in understanding the global disproportionate burden of PCa shared among Africans and other men of African descent. Nonetheless, disparities involved in diagnosis, treatment, and survival of PCa patients has also been correlated to socioeconomic status, education and access to healthcare. Although recent studies suggest equal PCa treatments yield equal outcomes among patients, data illuminates an unsettling reality of disparities in treatment and care in both, developed and developing countries, especially for men of African descent. Yet, even after adjusting for the effects of the aforementioned factors; racial disparities in mortality rates remain significant. This suggests that molecular and genomic factors may account for much of PCa disparities.

Genomic, epigenomic, and transcriptomic signatures of prostate cancer between African American and European American patients

“…Moreover, AA prostate cancer patients present with higher grade and stage tumors and have a nearly 2-fold higher mortality rate when compared to EA prostate cancer patients (2). Specifically, AA men have a prostate cancer mortality rate of 37.4 per 100,000 in the period of 2014-2018 versus 19.3 per 100,000 among white non-Hispanic men (3). Furthermore, prostate cancer has a higher growth and metastatic transformation rate for AA men compared to EA men (4).…”

Downregulation of miR-99b-5p and Upregulation of Nuclear mTOR Cooperatively Promotes the Tumor Aggressiveness and Drug Resistance in African American Prostate Cancer

“…A striking PCa disparity was observed, where African Americans (AAs) demonstrate a 1.7-fold higher incidence rate and a 2.3-fold higher mortality rate compared to their European American (EA) counterparts [ 1 ]. Besides the socioeconomic factors, accumulating genomic studies have suggested that genetic risk factors may also be involved in the PCa disparities [ 2 , 3 , 4 , 5 ]. MicroRNAs (miRNAs) are short non-coding RNAs regulating protein expression through degradation of target mRNAs or inhibition of protein translation.…”

Racial differences in serum chemokines in prostate cancer patients

“…Even after adjusting for nonbiological factors, prostate cancer mortality rates remain significantly higher in AA men than in CA. 6,7 A 5-year analysis revealed a 73% higher incidence rate and more than two times higher deaths due to prostate cancer in AA than in CA men. 2 Therefore, various biological factors, including the high systemic levels of inflammatory exposure associated with differential allostatic load, 8,9 may account for aggressive prostate cancer by altering tumor-specific immunobiology in AA men.…”