Study identifies nearly 90 new genetic variations that increase prostate cancer risk

A trans-ancestry genome-wide association meta-analysis of prostate cancer identified 86 new genetic risk variants independently associated with prostate cancer risk, according to findings published in Nature Genetics.^1,2

The researchers also found evidence supporting the role of germline variation in healthcare disparities related to prostate cancer. According to the analysis, the risk of developing prostate cancer inherited by men of African ancestry is approximately twice the risk inherited by men of European ancestry. The results also showed that men of Asian ancestry inherit approximately three-fourths the risk of prostate cancer as the risk inherited by men of European ancestry.

“We not only found new markers of risk, but also demonstrated that, by combining genetic information across populations, we were able to identify a risk profile that can be applied across populations,” corresponding author Christopher Haiman, ScD, professor of preventive medicine at the Keck School of Medicine of USC and director of the USC Center for Genetic Epidemiology, stated in a press release.¹ “This emphasizes the value of adding multiple racial and ethnic populations into genetic studies.”

Researchers at the USC Center for Genetic Epidemiology and the Institute of Cancer Research in London launched this study to better understand and address disparities in prostate cancer risk related to genetic factors. The multiancestry meta-analysis of prostate cancer genome-wide association studies included 107,247 cases and 127,006 controls.

“Including more than 200,000 men of European, African, Asian and Hispanic ancestry from around the world, the study is the largest, most diverse genetic analysis ever conducted for prostate cancer—and possibly for any other cancer,” according to the investigators.

The study’s identification of 86 new genetic risk variants brought the total number of known genetic risk variants independently associated with prostate cancer risk to 269.

The analysis showed that, “The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 for men of European ancestry to 3.74 for men of African ancestry,” the investigators wrote.

The estimated mean GRS for men of African ancestry was 2.18-times higher than the estimated mean GRS for men of European ancestry. In contrast, the estimated mean GRS for men of East Asian ancestry was 0.73-times lower than that for men of European ancestry.

“These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction,” the authors wrote in their conclusion.

Looking ahead, Haiman stated, “Our long-term objective is to develop a genetic risk score that can be used to determine a man’s risk of developing prostate cancer. Men at higher risk may benefit from earlier and more frequent screening, so the disease can be identified when it’s more treatable.”¹

The investigators believe a large-scale clinical trial would now be needed to examine how genetic risk score could contribute to better screening/early detection.

“Most important, unlike previous screening trials, this one would need to be more representative of the diversity we see in the world,” Haiman stated. “No population should get left behind.”¹

References

1. Largest, most diverse prostate cancer study shows genetic role in health disparities. Posted online January 4, 2020. https://bit.ly/2XlGQss. Accessed January 7, 2020.

2. Conti DV, Darst BF, Moss LC, et al. Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction. Nat Genet. 2021. doi: 10.1038/s41588-020-00748-0