Genomic alterations in prostate cancer appear to vary according to race
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Tumor genomic alterations appeared to differ among Black, white and Asian men with prostate cancer, according to results of a study published in The New England Journal of Medicine.
“There may be racial differences in genomic alterations that are associated with prognosis and response to therapy in prostate cancer and there are a number of potential causes of these differences, including variations in treatment, epigenetics driven by external factors and frequencies of these alterations across populations,” Brandon A. Mahal, MD, assistant professor of radiation oncology and assistant director of community outreach and engagement at University of Miami Sylvester Comprehensive Cancer Center, told Healio. “If genomic studies continue to fail to capture this diversity, the prognostic models and therapies developed from these studies could lead to greater disparities. As the field of oncology moves more toward precision medicine driven by genomics, there is potential to widen disparities if we continue to use Eurocentric cohorts in research.”
Mahal and colleagues sought to assess potential racial differences in tumor genomic profiling among a cohort of white (n = 2,109), Black (n = 204) and Asian (n = 80) men treated for prostate cancer at Memorial Sloan Kettering Cancer Center or Dana-Farber Cancer Institute. Among the 2,393 men, 1,484 had primary disease (white, n = 1,308; Black, n = 133; Asian, n = 43) and 909 had metastatic disease (white, n = 801; Black, n = 71; Asian, n = 37).
Researchers pooled tumor genomic data acquired through next-generation sequencing from the registry of American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (GENIE) version 7.0. They examined mutational profiles of 474 genes according to race and tumor stage and used the Benjamini-Hochberg method to control for false discovery rate.
Results showed that among those with primary disease, 11.5% of Asian men had more than 20 mutations. Researchers also found FOXA1 mutations occurred less often among white men (11.9%) than Black men (18.6%; percentage-point difference, 6.7; 95% CI, 0.8-13.5) and Asian men (37.8%; percentage-point difference, 25.9; 95% CI, 10.2-41.7). TP53 mutations occurred more frequently among white vs. Black men (20.6% vs. 14.2%; percentage-point difference, –6.4; 95% CI, –12.7 to 0).
Mutations in the gene encoding androgen receptor were uncommon across all races.
Among those with metastatic prostate cancer, 6.8% of Black men had more than 20 mutations. Mutations in the gene encoding androgen receptor occurred more frequently among Black vs. white men (18.3% vs. 8.1%; percentage-point difference, 10.2; 95% CI, 1-19.4). TP53 mutations were more common among Asian men (62%) than Black men (22.5%; percentage-point difference, 49.5; 95% CI, 21.2-58) and white men (36.4%; percentage-point difference, 25.6; 95% CI, 9.7-41.7).
In addition, Black men were more likely than white men to have genes with actionable mutations (26.7% vs. 18%; percentage-point difference, 8.7; 95% CI, 0-19.5) and mutations in DNA-repair genes (22.5% vs. 15.6%; percentage-point difference, 6.9; 95% CI, 0.5-18.1). BRAF mutations also were more common among Black vs. white men (7% vs. 1.5%; percentage-point difference, 5.5; 95% CI, 0.4-11.5).
“This study is important because it highlights how genomics, including the current way that genomics are studied, could impact prostate cancer disparities,” Mahal said. “In the era of precision medicine, this is a critical issue that could have major implications for patients. Future genomic and clinical trial studies must enroll more diverse patient populations to avoid the potential widening of disparities. Future work with larger numbers of minority patients and details on treatments and other exposures is needed to provide further insight into what may be driving the observed differences.”
For more information:
Brandon A. Mahal, MD, can be reached at University of Miami Sylvester Comprehensive Cancer Center, 5555 Ponce De Leon Blvd., Floor 1, Coral Gables, FL 33146; email: bmahal@miami.edu.
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