African men are known to have a much higher incidence of prostate cancer than other men. The largest new meta-analysis to date sheds light on why this is so, identifying nine new genetic variants that increase the risk of prostate cancer in African men.
In the UK, one in four African men will be diagnosed with prostate cancer during his lifetime. In the United States, an African-American man is 1.7 times more likely to be diagnosed with prostate cancer than a white man, and 2.1 times more likely to die from prostate cancer.
It is understood that genetic susceptibility plays a major role in the risk of developing prostate cancer. What is less well known is why men of African descent are particularly susceptible to the disease. To date, only small genome-wide association studies (GWAS) have been performed on these men to identify risk variants unique to African ancestry.
A new meta-analysis, led by researchers at USC’s Keck School of Medicine, conducted the largest-ever analysis of GWAS data to examine these risk factors. The researchers also developed a polyancestral polygenic risk score (PRS) that includes known and novel risk variants associated with prostate cancer risk and disease aggressiveness.
PRS shows how a person’s risk compares to others with different genetic makeup. It is usually calculated as the weighted sum of alleles associated with the trait. Alleles correspond to genes inherited from a biological parent occurring at a particular genetic site on the chromosome. Most traits are caused by more than one allele and some are controlled by more than one genetic locus.
Researchers pooled data collected from 10 GWAS conducted in the United States, Africa, and the Caribbean. This included data from over 80,000 men. 19,378 prostate cancer cases and he 61,620 healthy controls. They found nine previously unknown genetic risk factors for prostate cancer. Seven of them are more common or only found in African men.
One novel variant found in the 8q24 chromosomal region and known to be associated with prostate cancer susceptibility is found only in African men.
“This particular variant influences the risk of aggressive disease in this population,” said Christopher Haiman, corresponding author of the study.
The meta-analysis also confirmed the pattern seen in previous studies. This means that genetics play an important role in determining cancer risk in young men. It also highlights the need to include diverse populations in future large-scale genetic studies.
“Most of the studies to date have been conducted in populations of European ancestry, which has led to significant biases in our understanding of genetic risk for disease,” said Haiman.
The new genetic variants identified in this study can now be incorporated into genetic testing to help determine a person’s cancer risk and determine when and how often to get screened. His more accurate PRS for African men will help detect early those who are at increased risk of developing prostate cancer.
“Prostate cancer survival in men diagnosed with advanced disease is significantly lower,” said Fei Chen, Ph.D., the study’s first author. “Our findings suggest that these polygenic risk scores may help identify men who may benefit from early and more frequent screening.”
Hyman and his colleagues continue research on prostate cancer in African men, including how access to care and other social determinants affect prostate cancer incidence, progression, and survival. intend to do something.
The study was published in a journal european urology.
Source: USC Keck College of Medicine
