Genomic alterations may be linked to higher prostate cancer mortality among Black men
Black men with prostate cancer appeared to have a higher frequency of genetic alterations that may contribute to aggressive disease compared with their white counterparts, according to study results published in Molecular Cancer Research.
“Prostate cancer incidence and mortality are highest in African American men, but the exact reasons for the disparity are not fully understood,” Jianfeng Xu, DrPH, vice president of translational research at NorthShore University Health System, said in a press release. “The disparity is likely due to multiple factors, including socioeconomic differences and biology. We suspect that differences in the genetic changes that occur within tumors may play a critical role.”
Somatically acquired genetic alterations that could lead to higher prostate cancer incidence and mortality among Black men compared with white men remain mostly unknown.
Aggressive prostate cancer leads to the deaths of more than 33,000 men in the United States each year, including 5,350 Black men, according to study background.
Prostate cancer-specific death is usually caused by metastasis of cancer cells with driver genetic alterations traced back to prostate tumors.
Xu and colleagues used deeper next-generation sequencing to analyze the somatic mutations in 39 genes of 171 Black men and 860 white men. The researchers compared genetic alterations and sought to identify distinct irregularities that cause higher rates of mortality in Black men.
Results showed that more than 35% of Black men harbored damaging mutations in APC, ATM, BRCA2, KDM6A, KMT2C, KMT2D, MED12 and ZFHX3, all of which had more than 1% of mutated copies.
Among genes with more than 10% of mutated copies in tumor cells, ZMYM3 — a regulator of DNA repair and chromatin — was the most frequently mutated in Black men with prostate cancer. In a patient’s tumor with more than 96% frameshift mutations of ZMYM3, researchers observed allelic imbalances in 10 chromosomes, including losses of five and gains of four chromosomes. This suggests its role in maintaining genomic integrity.
Additionally, results showed prostate tumors of Black men had a higher frequency of copy number alterations of MYC, THADA, NEIL3, LRP1B, BUB1B, MAP3K7, BNIP3L and RB1 and a lower frequency of deletions of RYBP, TP53 and TMPRSS2-ERG than tumors of white men.
Deletion of MAP3K7, BNIP3L, NEIL3 or RB1 or gain of MYC is significantly associated with higher Gleason grade and advanced pathologic stage in Black men. Deletion of THADA is associated with advanced pathologic stage only.
The study’s small sample size served as a limitation.
“Our findings suggest that distinct genetic alterations in the prostate cancers of African American men, in comparison [with] white men, may contribute to more aggressive prostate cancer and could lead to a higher mortality rate,” Xu said in a press release. “If confirmed in other studies, these results will not only help to understand the racial disparity of prostate cancer, but could also help guide personalized clinical management, such as predicting prognosis and guiding targeted therapy.”
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