Study identifies 187 novel genetic variants associated with prostate cancer

Investigators have uncovered 187 novel genetic risk variants for prostate cancer, increasing the number to 451 total, based on findings from a multi-ancestry genome-wide study recently published in Nature Genetics.¹

“We’ll continue to improve this risk score and look for markers that help to distinguish aggressive from less aggressive disease," says Christopher A. Haiman, ScD.

In addition to the 187 new variants identified, the investigators also found 150 variants from known risk regions that had been replaced by a more significant lead variant.

Further, the results from externally replicated multi-ancestry genetic risk scores (GRSs) showed risks that ranged from 1.8 (per standard deviation) among men of African ancestry to 2.2 among men of European ancestry. Men of African ancestry were shown to have a greater risk of aggressive vs non-aggressive disease (P = .03).

Overall, the study included genomic data from 156,319 patients with prostate cancer and compared that with data from 788,443 controls, including nearly all studies on genomic variants linked with a risk of prostate cancer. The study builds on research from 2021 that identified 269 genetic variants correlated with prostate cancer risk.²

Compared with the 2021 study, the recent analysis demonstrated an 87% increase in the number of patients of African ancestry, a 45% increase in the number of patients of Latino ethnicity, a 43% increase in the number of patients of European ancestry, and a 26% increase in the number of patients of Asian ancestry.

Notably, the study also represents a 57% increase in the number of non-European participants compared with previous prostate cancer genome-wide association studies.

“We’re not going to learn everything there is to know about the genetics of prostate cancer by studying only White men. Larger and larger studies, engaging a broader spectrum of populations, are important if we’re going to identify genetic markers of risk and develop risk prediction tools that are equally effective across populations,” said co-senior author Christopher A. Haiman, ScD, in a news release on the findings.³ Haiman is the AFLAC Chair in Cancer Research and a professor of population and public health sciences at the Keck School of Medicine at the University of Southern California in Los Angeles.

Based on the data, the investigators also noted a 3% (Asian), 14% (European), 15% (Hispanic), and 23% (African) increase in the odds ratio (per standard deviation) for the GRS with all 451 variants compared with the previous GRS with 269 variants.

Altogether, the study efforts included over 300 investigators across 100 institutions in 26 nations. The authors indicated that further work remains.

“We’ll continue to improve this risk score and look for markers that help to distinguish aggressive from less aggressive disease. Clinical trials will be required to evaluate the effectiveness of the risk score in helping doctors and patients make decisions about screening,” Haiman concluded in the news release.³

References

1. Wang A, Shen J, Rodriguez AA, et al. Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants. Nat Genet. 2023. doi:10.1038/s41588-023-01534-4

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;53(1):65-75. doi:10.1038/s41588-020-00748-0

3. 187 new genetic variants linked to prostate cancer found in largest, most diverse study of its kind. News release. Keck School of Medicine of USC. November 9, 2023. Accessed November 10, 2023. https://keck.usc.edu/187-new-genetic-variants-linked-to-prostate-cancer-found-in-largest-most-diverse-study-of-its-kind/