The RESPOND study is a research effort to identify the factors underlying the disproportionate prostate cancer outcomes faced by African American men compared with other ethnicities in the US. One component of RESPOND was a genetic risk factor meta-analysis, the findings of which were published in European Urology.
Researchers, led by first author, Fei Chen, identified 9 novel genetic loci associated with prostate cancer susceptibility. Of these, 7 were only found or significantly more common in men of African ancestry, and authors noted 1 was an African-specific stop-gain variant in the prostate-specific gene anoctamin 7 (ANO7).
Prostate Cancer Risk Variants in African American Men
Investigators incorporated the novel susceptibility loci with known risk variants and developed a multiancestry polygenic risk score (PRS) based on 278 genetic factors to predict risk of prostate cancer and aggressive or nonaggressive disease.
The meta-analysis included 10 genome-wide prostate cancer association studies that encompassed 19378 men of African ancestry with prostate cancer and 61620 controls. Researchers evaluated their multiancestry PRS model for associations with prostate cancer disease outcomes.
According to the authors, the PRS was strongly associated with prostate cancer risk in African ancestry studies. Specifically, the PRS assigned 3- and 5-fold increased odds ratios (ORs) for the top 10% and 1% of scores, respectively. More notably, men in the top PRS decile had significantly greater risk for aggressive prostate cancer compared with men in the 40-60% PRS percentile (OR, 1.23; 95% CI, 1.10-1.30; P=.00044).
“In this large genetic study in men of African ancestry, we discovered nine novel prostate cancer (PCa) risk variants,” Chen and colleagues summarized. “We also showed that a multiancestry polygenic risk score was effective in stratifying PCa risk, and was able to differentiate risk of aggressive and nonaggressive disease.”
The RESPOND study is ongoing, and is funded by the National Cancer Institute, the National Institute on Minority Health and Health Disparities, and the Prostate Cancer Foundation.