The largest-ever study of prostate cancer genetics in black men has uncovered nine previously undiscovered variants that raise risk in this population. Seven of these variants are found either largely or exclusively in men of African descent.
The study was led by Christopher Haiman, ScD, director of the Center for Genetic Epidemiology at the Keck School of Medicine of USC. The report was published in European Urology.
One in six Black men in the United States will be diagnosed with prostate cancer in his lifetime versus one in eight white men. Black men are more likely to be diagnosed at a younger age, with more aggressive disease, and are more than twice as likely to die of prostate cancer.
Previous studies have identified close to 270 genetic variants linked to prostate cancer risk, but while there is a lot of work on biomarkers for this population, so far these findings do not explain the disproportionate risk among men of African ancestry. Nor have they been able to predict which Black men face a high risk for aggressive prostate cancer.
This team’s meta-analysis of 10 genome-wide association studies pooled data representing more than 80,000 men of African ancestry (19,378 men with prostate cancer and 61,620 healthy controls) collected in the United States, Africa, and the Caribbean.
The researchers found nine previously undiscovered genetic variants that increased the risk of prostate cancer in these men. One new variant in the 8q24 region, long known to influence prostate cancer risk, is found only in men of African ancestry and may be linked to higher rates of aggressive disease in this population.
This team also showed that a multi-ancestry polygenic risk score was able to differentiate between the risks of developing aggressive and nonaggressive prostate cancer in men of African ancestry.
The newly identified variants can be used to refine polygenic risk scores. These are genetic tests that assess a person’s risk for developing a condition based on the combined influence of multiple genetic factors and can help patients decide how early and often to get screened.
As the authors wrote, “This study … suggests a potential clinical utility of PRS in differentiating between the risks of developing aggressive and nonaggressive disease in men of African ancestry.
Haiman and collaborators research prostate cancer among Black men through the $26.5 million, multi-center RESPOND (Research on Prostate Cancer in African American Men: Defining the Roles of Genetics, Tumor Markers, and Social Stress) study, funded by the Prostate Cancer Foundation (PCF), the National Cancer Institute, and the National Institute on Minority Health and Health Disparities.
His team’s work includes research into how social determinants, access to care, genetics, and tumor characteristics affect prostate cancer diagnosis, progression, recurrence, and survival rates.
Haiman and colleagues also are now working to develop a Polygenic Risk Test for Prostate Cancer, a non-invasive, early detection test that will identify a man’s lifetime prostate cancer risk using a combination of the nearly 270 genetic variants obtained from a single sample of saliva or blood.