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

Men of African descent are known to have a much 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 descent.

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

It is understood that genetic susceptibility plays an important role in the risk of developing prostate cancer. What is not well known is why men of African descent are particularly vulnerable to the disease. So far, only small genome-wide association studies (GWAS) have been undertaken on these men with the aim of identifying risk variants specific to African ancestry.

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

A PRS tells you how a person’s risk compares to others with a different genetic makeup. It is usually calculated as a weighted sum of trait-associated alleles, which correspond to 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 genetic sites.

The researchers pooled data collected from 10 GWAS companies in the United States, Africa and the Caribbean, which included data from more than 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 or found exclusively in men of African descent.

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

“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 trends seen in previous studies that genetics play a crucial role in determining cancer risk in younger men. It also highlights the need to include diverse populations in future large-scale genetic studies.

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

The identification of new genetic variants through study can now be incorporated into genetic testing to help determine a person’s cancer risk and guide the timing and frequency of screening. A more accurate PRS for men of African descent would help in the early identification of people at high risk of developing prostate cancer.

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

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

The study was published in the journal European Urology.

Source: USC Keck School of Medicine

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