Largest study of its kind finds new genetic links to prostate cancer

Men of African descent are known to have a far higher incidence of prostate cancer than other men. A new meta-analysis, the largest to date, has shed light on why this is so, identifying nine new genetic variants that increase the risk of prostate cancer in men of African ancestry.

In the UK, one in four men of African descent will be diagnosed with prostate cancer in their lifetime. In the US, African American men are 1.7 times more likely to be diagnosed with – and 2.1 times more likely to die from – prostate cancer than white men.

It’s understood that genetic susceptibility plays a large role in the risk of developing prostate cancer. What’s not well known is why men of African descent are particularly vulnerable to the disease. Before now, only small genome-wide association studies (GWASs) have been undertaken on these men in an attempt to identify African-ancestry-specific risk variants.

A new meta-analysis led by researchers at the Keck School of Medicine of USC undertook the largest-ever analysis of GWAS data to examine these risk factors. The researchers also developed a multiancestry polygenic risk score (PRS) comprising known and new risk variants associated with prostate cancer risk and disease aggressiveness.

A PRS tells you how a person’s risk compares to others with different genetic makeup. It is typically calculated as a weighted sum of trait-associated alleles, which are matching genes inherited from biological parents that occur at a given gene site on a chromosome. Most traits are caused by more than two alleles, and some traits are controlled by two or more gene sites.

The researchers pooled the data collected from 10 GWASs undertaken in the US, Africa and the Caribbean which included data from over 80,000 men: 19,378 prostate cancer cases and 61,620 healthy controls. They discovered nine previously unknown genetic risk factors for prostate cancer, seven of which are more common to, or found exclusively in, men of African descent.

One new variant, found on the 8q24 chromosome region and known to be associated with prostate cancer susceptibility, is only found in men of African ancestry.

“This particular variant is influencing the risk of aggressive disease in this population,” said Christopher Haiman, corresponding author of the study.

The meta-analysis also confirmed patterns seen in previous studies, namely that genetics plays a crucial role in determining cancer risk in younger men. It also highlights the need for including diverse populations in future large-scale genetic studies.

“The vast majority of studies to date have been conducted in populations of European ancestry, which creates a huge bias in our understanding of genetic risk for disease,” Haiman said.

The study’s identification of new genetic variants can now be incorporated into genetic testing to help determine a person’s cancer risk and guide how early and how often they get screened. More accurate PRS for men of African descent would assist with the early identification of those at high risk of developing prostate cancer.

“Prostate cancer survival is significantly lower among men diagnosed with aggressive disease,” said Fei Chen, PhD, lead author of the study. “Our findings suggest that these polygenic risk scores could be useful for identifying men who may benefit from earlier and more frequent screenings.”

Haiman and his colleagues plan to continue their research into prostate cancer amongst men of African ancestry, including how access to care and other social determinants influence the incidence, progression and survival rates of the disease.

The study was published in the journal European Urology.

Source: Keck School of Medicine of USC

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