NEW YORK – In a comparative genomic analysis, researchers uncovered distinct genomic profiles among prostate tumors isolated from African-American and European-American men.
Prostate cancer is common among men, with nearly 175,000 new cases each year in the US. But African-American men are more likely than European-American men to develop prostate cancer, and when they do, they have a higher mortality rate.
Previous studies have suggested there might be genomic differences in the tumors found among African-American and European-American men, so an Icahn School of Medicine at Mount Sinai-led team conducted a retrospective analysis of tumors from more than a thousand men to examine differences in gene expression or affected biological pathways between the groups. As they reported in the journal Communications Biology this week, the researchers uncovered distinct genomic differences that could influence how prostate cancer should be managed clinically and that could, in part, explain disease disparities.
"Racial disparity in prostate cancer is a significant problem," senior author Ashutosh Tewari, a urologist at Mount Sinai, said in a statement. He added that he and his colleagues found that "tumor characteristics (or tumor genomic factors) were substantially different" between African-American men and European-American men.
The researchers analyzed a cohort of 1,152 men, 596 of whom were African American and 556 of whom were European American, and all of whom had undergone radical prostatectomy. Overall, African-American men had higher pre-treatment prostate-specific antigen levels and higher scores indicating increased risk of post-surgery recurrence, emphasizing the more aggressive disease generally found among African-American men.
By examining differences in gene expression between the groups, the researchers found tumors from African-American men were more likely to have higher expression of immune response-, hypoxia-, and apoptosis-related genes and decreased expression of mismatch repair genes, as compared to tumors from European-American men.
In particular, inflammation genes like IL33, IFNG, CCL4, CD3, and ICOSLG were upregulated among samples from African-American patients, while DNA mismatch repair genes like MSH2 and MSH6 were downregulated. MSH2 and MSH6, the researchers noted, were also downregulated among African-American men with prostate cancer in The Cancer Genome Atlas dataset. They also noted differences in SPINK1 expression.
This finding of decreased DNA mismatch repair gene expression, the researchers noted, could affect how tumors from African-American men respond to radiation therapy. At the same time, they uncovered differences in response to chemotherapy between the men. Based on cell line analyses, they suggested that African-American men may better respond to DNA damage and alkylating agent-based chemotherapy, while white men may better respond to anti-microtubule-based chemotherapy. Both findings need to be followed up in clinical trials, the researchers said, but underscores the need to better personalize treatments.
Overall, the researchers said that their findings suggest that African-American men who undergo radical prostatectomy should be closely monitored following treatment, as they are generally at increased risk for recurrence.
They cautioned, though, that their study has several limitations, including its retrospective design and descriptive nature. It further does not take into account differences in socioeconomic and other factors that may differ between African-American men and European-American men that influence racial disparities in prostate cancer, they noted.