Genomic Profiles of Prostate Cancers Differ Between Men of African and European Ancestry

By Will Boggs MD

August 11, 2020

NEW YORK (Reuters Health) - The genomic profiles of prostate cancers in African-American men and men of European ancestry show several differences, researchers report.

"This study strongly supports the idea that samples from African-American patients need to be included in future molecular studies and clinical trials for new prostate-cancer therapies," Dr. Joshua D. Campbell of Boston University School of Medicine told Reuters Health by email.

African-American men have a higher incidence of prostate cancer, present with more advanced disease at an earlier age, and have increased mortality from the disease compared with European Americans. Whether genomic alterations differ between these groups and contribute to clinical outcomes remains unclear.

Dr. Campbell, also at Broad Institute of MIT and Harvard, in Cambridge, Massachusetts, and colleagues evaluated prostate-cancer genomic alterations associated with race and investigated tumor genomic features in primary and metastatic disease in 250 African-American men and 611 European-American men from four publicly available data sets.

Tumors from African-American men showed significantly higher frequencies of somatic mutations in ZFHX3 (6.0% vs. 2.1%), ETV3 deep deletions (6.3% vs. 2.3%), and deletions in ZFHX3 (8.8% vs. 3.4%) and NKX3-1 (10.5% vs. 5.4%).

In contrast, deletions in PTEN were significantly less common in African-American men (5.3%) than in European American men (15.3%), the researchers report in Clinical Cancer Research.

In a separate analysis of 3,454 men with localized and metastatic prostate cancer, frequencies of several genomic alterations were significantly higher in tumors from African-American men than in European-American men, including CCND1 amplification, HGF amplification, KMT2D truncation, MYC amplification, SPOP point mutation, and overall alterations in KEL, NOTCH2, and PTCH1.

There were no significant differences between African-American and European-American men in currently clinically actionable genes.

"We were able to find genes that were more frequently mutated in prostate cancers from African-American patients including ZFHX3, ETV3, and MYC," Dr. Campbell said. "These associations had not been previously reported, although other studies had already found that some genes were less frequently mutated in tumors from this population (e.g., the TMPRSS2-ERG fusion and PTEN deletions)."

"We found that the frequency of mutations in DNA repair genes and other genes that are targets of current therapeutics are similar between men with African ancestry compared to other groups," he said. "This suggests that current prostate-cancer therapies should be beneficial in people of both African and European ancestry as long as they are applied equitably."

Dr. Timothy Rebbeck of Harvard T. H. Chan School of Public Health and Dana Farber Cancer Institute, in Boston, who earlier reviewed variation in prostate-cancer genetics by race, ethnicity and geography, told Reuters Health by email, "We have known for a while that there are differences in genomic features of prostate tumors. The fact that this study reported differences is therefore consistent with the literature, but it was interesting to see in this paper that many of the clinically relevant molecular events do not differ by race."

"This work needs to be confirmed before the data can be translated to clinical practice, but if there are similarities in molecular profiles across races for relevant therapies, this could guide therapeutic decisions," said Dr. Rebbeck, who was not involved in the new research. "However, these data don't provide data on treatment responses, so studies that extend these molecular differences to actual treatment responses or outcomes still need to be done."

SOURCE: Clinical Cancer Research, online July 10, 2020.