Genetic Alterations Discovered in Hispanic Men With Prostate Cancer

A study published in The Prostate revealed discrepancies in gene alterations occurring in Hispanic men with prostate cancer (PCa). This research addresses an important demographic gap in the literature on Hispanic men with PCa.

In the United States, PCa is the most prevalent form of cancer affecting Hispanic and Latino men, as well as the number 1 cause of cancer death for men in Latin American countries. Despite this reality, research on the pervasiveness and implications of altered DNA in Hispanic men—and their associations with PCa—is still relatively understudied.

Researchers gathered information from the Memorial Sloan Kettering Cancer Center (MSK) to observe patient samples of primary and metastatic adenocarcinomas. Men with targeted next-generation sequencing genomic profiles were identified and any gene was considered “altered” if it exhibited at least 1 reported point mutation, structural variant, or copy number alteration. Hispanic White and non-Hispanic White categories were also created after analyzing available ethnicity and primary race data from a plethora of contributing institutions.

Data from MSK included 1412 samples of primary tumors (n = 78 Hispanic White; n = 1334 non-Hispanic White) and 818 samples of metastatic tumors (n = 40 Hispanic White; n = 778 non-Hispanic White).

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Results from primary tumor analysis evaluated 465 genes and revealed statistically significant differences in 10 genes between the 2 groups. Hispanic White men had higher alteration frequencies compared to non-Hispanic White men in the TMPRSS2 gene (51.28% vs 31.86%; P = .0007; odds ratio [OR], 0.44), ERG (42.31% vs 25.34%; P = .002; OR, 0.46), PPARG (4.69% vs 0.30%; P = .003; OR, 0.06), PMAIP1 (2.56% vs 0.07%; P = .008; OR, 0.03), SOX9 (3.85% vs 0.60; P = .019; OR, 0.15), and the NTHL1 gene (3.12% vs 0.20%; P = .02; OR, 0.06).

In the metastatic tumor analysis, 465 genes were also evaluated and statistically significant differences were observed in 7 genes. Hispanic White men had more alterations in the CCNE1 gene (10.00% vs 1.29%; P = .003; OR, 0.12), SH2D1A (5.00% vs 0.26%; P = .013; OR, 0.05), KRAS (7.50% vs 1.03%; P = .014; OR, 0.13), NEGR1 (8.11% vs 1.21%; P = .016; OR, 0.14), and STK11 gene (5.00% vs 0.39%; P = .021; OR = 0.07).

The total number of actionable mutations and total mutations in DNA repair genes was higher in metastatic samples than primary tumors. However, there were no statistically significant differences in prevalence between the 2 cohort groups.

The authors believed that their small cohort size made it difficult to fully assess race- and ethnicity-specific tumor diversity. Despite this limitation, they emphasize the importance of their research as the first to investigate the genomic patterns of Hispanic men with metastatic and primary PCa tumors.

Although racial and ethnic differences cannot fully explain patient outcomes, the researchers stress how meaningful future studies can be for understanding the extent to which genetics influence PCa behavior. They hope their study sparks interest in further research on non-White and non-European populations, and the implications that gene-targeting therapies, prostate-specific antigen levels, cancer grade, and stage have on assessing potential risks for certain patients.

Reference

Arenas-Gallo C, Rhodes S, Garcia JA, et al. Prostate cancer genetic alterations in Hispanic men. Prostate. Published online June 10, 2023;83(13):1263-1269. doi: 10.1002/pros.24586