Gene Variants May Advance Cancer Precision Medicine for Black Men

July 14, 2020 - Newly identified gene variants could possibly lead to precision medicine prostate cancer therapies specifically for black men.

Black men in the US are known to disproportionately suffer from prostate cancer, the researchers noted. While cancer mortality rates in the US have declined, disparities by race have persisted. One in every six black Americans will be diagnosed with prostate cancer in their lifetime, and these men are twice as likely to die from the disease as men of other races.

However, few studies have investigated whether genetic differences in prostate tumors could have anything to do with these health disparities.

To date, studies that try to figure out what genes are commonly mutated in prostate cancers often have had very few samples from racial and ethnic minority groups despite the greater burden of prostate cancer in those populations.

As more genetic health studies are performed in minority populations, it’s become increasingly clear that other genetically targeted therapies that were developed based on studies of patients of European descent are at times much less effective in minority populations. These therapies can also cause dangerous side effects in other racial and ethnic groups.

Researchers from Boston University School of Medicine (BUSM), UC San Francisco (UCSF), and Northwestern University set out to better understand differences in the mutations driving prostate cancer tumors in black Americans compared to European Americans, and whether any such differences could influence disease outcomes or the effectiveness of targeted therapies.

The team collected and analyzed DNA sequencing data from previously published studies and from a commercial molecular diagnostics company. In total, they examined the mutational patterns in prostate cancers from more than 600 black men, representing the largest study of this population to date.

Researchers found that the frequency of mutations in DNA repair genes and other genes that are targets of current therapeutics are similar between the two groups, indicating that at least these classes of current precision prostate cancer therapies should benefit people of both African and European ancestry.

Although the team did not find significant differences in frequencies of mutations in genes important for current prostate cancer therapies, they did identify other genes that were more frequently mutated in prostate cancers from black men.

"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 co-corresponding author Joshua Campbell, PhD, assistant professor of medicine at BUSM.

The results demonstrate the need for studies to analyze the different factors that impact cancer severity in different populations, researchers said.

"The poorer health outcomes we see in Black men with prostate cancer are not easily explained by any of the distinct gene mutations we identified in prostate tumors from men of African ancestry," said Franklin Huang, MD, PhD, an assistant professor in UCSF's Division of Hematology/Oncology and member of the UCSF Helen Diller Family Comprehensive Cancer Center, UCSF Institute for Human Genetics, and UCSF Bakar Computational Health Sciences Institute.

"This highlights the need to examine the environmental and social inequities that are well known to influence health outcomes across the board. On the other hand, our tumor genomic analysis also showed that current precision medicine approaches ought to be as effective in Black Americans as they have been for other groups -- if we can ensure that these drugs are applied equitably going forward."

Understanding how tumor genomics and other biological factors interact with social and environmental inequities to drive poorer health outcomes for black prostate cancer patients should be top priority to accelerate precision medicine for this population, the team said.

"These types of studies will remain important to understand when certain therapies may preferentially benefit Black patients, who continue to remain underrepresented in clinical trials," Campbell said.

Specifically, the results will inform the efforts of NCI’s RESPOND study, which aims to recruit 10,000 black prostate cancer patients to better understand the drivers of the disease’s burden among black populations.

"Previous studies have looked in isolation at different biological, social and environmental drivers of well-known racial disparities in prostate cancer," Huang said. "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."