Prostate cancer mortality is twice as high among Black men as White men, a disparity likely due to inherited genetics, modifiable cancer risk factors, and healthcare access. A study published in Clinical Cancer Research sought to elucidate how and why tumor genomes differ by self-reported race and genetic ancestry.
Researchers assessed 2,069 men with prostate cancer (1,841 self-reported White, 63 Asian, and 165 Black patients) with access to clinical-grade sequencing at the same cancer center. They analyzed the prevalence of tumor and germline alterations in cancer driver genes reported to have different alteration prevalence by race.
Clinical characteristics such as prostate-specific antigen and age at diagnosis as well as cancer stage at sample procurement differed by self-reported race. However, most genomic differences persisted when adjusting for clinical characteristics. Tumors from Black men harbored fewer PTEN mutations and more AR alterations than those from White men. Tumors from Asian men had more FOXA1 mutations and more ZFHX3 alterations than White men. Despite fewer TP53 mutations, tumors from Black men had more aneuploidy, particularly chromosome arm 8q gains, an adverse prognostic factor. Genetic ancestry was associated with similar tumor alterations as self-reported race, but also with modifiable cancer risk factors. Community-level average income was associated with chromosome arm 8q gains after adjusting for race and ancestry.
“Tumor genomics differed by race even after accounting for clinical characteristics. Equalizing access to care may not fully eliminate such differences. Therapies for alterations more common in racial minorities are needed. Tumor genomic differences should not be assumed to be entirely due to germline genetics,” the researchers concluded.