African American, European Ancestry Men Benefit from Same Targeted Prostate Cancer Therapies

African American, European Ancestry Men Benefit from Same Targeted Prostate Cancer Therapies

A large prostate cancer genomics study suggests African-American men, who are disproportionately affected by the cancer, should also benefit from current therapies that target specific genetic mutations causing the disease.

However, the researchers—based at Boston University School of Medicine, University of California San Francisco, and Northwestern University—did discover some genetic differences between the cancers from European Americans and African Americans, which they believe warrants further investigation.

African-American men have a 15% chance of developing prostate cancer compared with a 10% chance for European-American men. They are more likely to develop aggressive disease and are twice as likely to die from the cancer than White men. It is possible that this inequality may be due to socio-economic status and healthcare disparities, but genetic differences in cancer mutational status could also be responsible.

In what they claim is the largest such study to date, the researchers studied mutations linked to prostate cancer in 250 African American and 611 European American men from four publicly available datasets. They then compared these to prostate cancer mutations found in 436 African American and 3018 European American men with both localized and metastatic prostate cancer who contributed samples to the Foundation Medicine commercial cohort.

As reported in the journal Clinical Cancer Research, the team found no notable differences in genetic variation that would impact the efficacy of current therapies for prostate cancer, such as treatment with PARP inhibitors targeting DNA repair genes, between the two groups of men.

However, they did find some genetic differences between the two groups. For example, two genes linked to prostate cancer suppression, ETV3 and ZFHX3, were more often mutated in African-American men with prostate cancer than in European Americans. The MYC gene, which is often overexpressed in cancers, was also more often amplified in African-American men with metastatic prostate cancer.

“These results reinforce the idea that there can be biological differences in prostate cancers between different ancestral groups and that samples from Black Americans need to be included in future molecular studies to fully understand these differences,” said Joshua Campbell, PhD, an assistant professor at Boston University School of Medicine who is one of the study authors.

The differences in rates of onset and outcome of prostate cancer has been recognized before and in 2018 the RESPOND study was set up by the US National Institute of Health to investigate this issue further. It aims to enroll 10,000 African-American men with prostate cancer and will investigate whether environmental issues, genetic differences, or both are responsible for the higher rates and more aggressive disease seen in these men.

“Previous studies have looked in isolation at different biological, social and environmental drivers of well-known racial disparities in prostate cancer,” said Franklin Huang, MD, PhD, an assistant professor at UCSF and corresponding author on the current study. “RESPOND is a nationwide effort to integrate all these components and ultimately identify specific steps that can be taken to eliminate prostate cancer’s unequal burden in Black communities.”