Genomic Profiling is Important to Address Racial Disparities in Prostate Cancer

With Black Americans known to have a higher incidence and mortality rate for prostate cancer, a new report published in Cancer Reports aimed to explore solutions and novel immunotherapies to address these disparities.

African Americans in the United States have higher incidences and mortality rates for many cancers, with a lifetime risk of prostate cancer at 1 in 6 and a lifetime risk of prostate cancer-specific mortality of 1 in 23. Non-Hispanic whites have a lower risk of prostate cancer with an incidence of 1 in 8 and a mortality of 1 in 42.¹

“We provide a comprehensive review of the significant research in recent years that has examined the molecular and genomic reasons for unequal cancer burden in African American and Caucasian American populations and acknowledge the challenges that lie ahead,” said senior author Ashutosh K. Tewari, MD, of the Icahn School of Medicine at Mount Sinai, in a press release. “This article provides specific guidelines for managing prostate cancer in African American men based on their disease’s biology and makes a significant contribution to the ongoing national effort to improve African American men’s outcomes from prostate cancer.”²

According to the report, the main drivers of these disparities include socioeconomic factors leading to lifestyle and dietary issues, health care access problems, and potentially tumor biology. Researchers proposed that a deeper understanding of both clinical and molecular differences can facilitate improved outcomes in African American men. The report authors noted that clinicians debate which of these factors is the most significant, but recent research has found that once socioeconomic differences are removed, prostate cancer mortality rates for African American and Caucasian men are similar.¹

Recent research has outlined molecular differences in prostate cancer between Black and Caucasian men, including genetic polymorphisms, gene mutations, epigenetic changes, and microRNAs. In their research, investigators Hanahan and Weinberg outlined Hallmarks of Cancer, including constitutive proliferation, overriding cell death, uncontrolled cell division, tumor invasion and metastatic cascade, metabolic reprogramming, genetic variations and chromosomal instability, pro-tumor inflammation, and tumor microenvironment.¹

When examining specific findings in African American men, Hanahan and Weinberg listed specific findings for each hallmark. For example, when discussing constitutive proliferation, Black men exhibit defective androgen receptor signaling, such as a high frequency of androgen receptor-specific germline and somatic hypermutations and CYP17 and CYP3A4 gene polymorphisms. Understanding such genetic differences is essential in order to properly treat and manage prostate cancer in Black men.¹

Other research has explored potential anatomical differences and molecular correlations in prostate cancer between Black and Caucasian men. A retrospective cohort of nearly 300 men confirmed previous findings that ETS-positive tumors were more common in Caucasian men, whereas SPINK overexpression was more common among Black men. Similarly, they found that anterior location was more common in Black men who were defined as low risk preoperatively.¹

With these findings in mind, the report authors discussed several actionable ideas. Prevention is especially important and can be addressed by improving issues such as housing security, job discrimination, and economic insecurity, the researchers noted. These insecurities often result in riskier dietary, lifestyle, and social behaviors, although epidemiological studies analyzing these issues have tended to focus on Caucasian populations, according to the report.¹

Some researchers, however, have found genomic abnormalities in prostate cancer with links to obesity, hypertension, and diabetes in African American men. Powell et al. used microarray methods to assess RNA expression levels of 517 genes known to be linked with prostate cancer. They listed 22 genes in African American men with the most significantly differential RNA expression, illustrating the intersection of prostate cancer with dietary and social behaviors in Black men.¹

The report authors also emphasized the importance of including Black men in prostate cancer clinical trials. This has historically been a challenge, they noted, and the statistics do not seem to be improving. A recent study showed that the percentage of African American men has reduced from 11.3% in 1995 to 2.8% in 2014, and in reviewing 51 trials from 1987, the researchers found that 96% of those recruited were non-Hispanic White men.¹

“Understanding the specific biology of prostate cancer in African American men and integrating clinical and genomic data will enable a ‘precision medicine’ approach to treating African American men and contribute to the ongoing efforts to improve outcomes in this population,” said co-author Sujit S. Nair, PhD, in the press release.²

REFERENCES

• Dovey Z, Nair S, Chakravarty D, Tewari A. Racial disparity in prostate cancer in the African American population with actionable ideas and novel immunotherapies. Cancer Reports; February 17, 202 https://onlinelibrary.wiley.com/doi/full/10.1002/cnr2.1340. Accessed February 22, 202
• Addressing the biological causes of racial disparities in prostate cancer [news release]. EurekAlert; February 18, 2021. https://www.eurekalert.org/pub_releases/2021-02/w-atb021621.php. Accessed February 22, 2021.