African Ancestry Is Linked With Higher Prostate Cancer Risk Vs European Ancestry

Christopher Haiman, ScD

Germline variation could play a role in racial disparities related to prostate cancer risk, with individuals of African descent having a higher mean genetic risk score (GRS) compared with men of European ancestry, according to a meta-analysis of prostate cancer genome-wise association studies conducted by researchers from the University of Southern California (USC) Norris Comprehensive Cancer Center.¹

Results showed that the top GRS decile associated with odds ratio was 5.06 for men of European descent (95% CI, 4.84-5.29) and 3.74 for men of African descent (95% CI, 3.36-4.17). When compared with men of European ancestry, men of African ancestry were estimated to have a mean GRS that was 2.18 times higher (95% CI, 2.14-2.22), while men of East Asian ancestry had a mean GRS that was 0.73 times lower (95% CI, 0.71-0.76).

“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,” said Christopher Haiman, ScD, professor of preventative medicine and AFLAC Chair in Cancer Research at the Keck School of Medicine of USC, and director the USC Center for Genetic Epidemiology.² “This emphasizes the value of adding multiple racial and ethnic populations into genetic studies.”

Additionally, investigators identified 86 new genetic risk variants, all of which were found to be independently associated with prostate cancer risk, which brings the total known risk variants to 269.

“To understand the aggregate effect of the 269 variants on prostate cancer risk, we constructed a GRS using the multiethnic weights of the risk variants associated with disease,” wrote the study authors. “Compared with men at average genetic risk in the 40% to 60% GRS category, the estimated odds ratio for men in the top 10% of the GRS [90%-100% GRS category] was 5.06 [95% CI, 4.84-5.29] for men of European ancestry, 3.74 [95% CI, 3.36-4.17] for men of African ancestry, 4.47 [95% CI, 3.52-5.68] for men of East Asian ancestry, and 4.15 [95% CI, 3.33-5.17] for Hispanic men. Men in the top 1% of the GRS distribution had higher odds of disease, ranging from 11.65 [95% CI, 10.56-12.85] for men of European ancestry to 5.68 [95% CI, 4.44-7.28] for men of African ancestry.”

Prior research has shown that certain races not only trend towards higher incidences of prostate cancer, but higher rates of disease-related mortality overall. Incidence rates of prostate cancer from 2012 to 2016 indicated that 172.9 non-Hispanic Black men per 100,000 develop prostate cancer compared with 97.2 non-Hispanic White men, 86.8 Hispanic men, 68 American Indian and Alaska Native men, and 52.9 Asian and Pacific Islander men.³

Similarly, mortality rates from 2013 to 2017 indicate that 38.7 non-Hispanic Black men per 100,000 died from prostate cancer vs 18.7 American Indian and Alaska Native men, 18 non-Hispanic White men, 15.7 Hispanic men, and 8.6 Asian and Pacific Islander men.

Despite the increased risk of incidence and death seen in Black patients, White patients are often overrepresented in clinical cancer trials, hindering investigators' progress in identifying reasons for these disparities.

This developed the rationale for the meta-analysis, with researchers from the USC Center for Genetic Epidemiology, as well as the Institute for Cancer Research in London, United Kingdom, striving to identify the reasons for these disparities. Investigators compiled data from the majority of global genomic prostate cancer studies, including 234,253 men of different races and ethnicities from the United States, United Kingdom, Sweden, Japan, and Ghana, consisting of 107,247 cases and 127,006 controls.

In what is considered the largest and most diverse genetic prostate cancer analysis, findings point toward genetics playing a role in the disparities seen across different racial groups, which could possibly help physicians apply precision medicine to early prostate cancer detection in the future.

“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,” said Haiman. “Men at higher risk may benefit from earlier and more frequent screening, so the disease can be identified when it’s more treatable.”

Current prostate cancer screening guidelines recommend that men aged 55 years or older with average risk undergo prostate-specific antigen (PSA) testing. Though high PSA levels are indicative of prostate cancer, this method typically detects more indolent tumors, leading to unnecessary treatment, according to investigators.

Additionally, investigators believe that GRS could help to guide more selective PSA testing by helping to identify patients who are at a higher risk for prostate cancer, potentially including high-risk patients younger than 55 years old. A larger clinical trial is needed in order to better translate these findings into improved early prostate cancer detection, investigators noted.

“Most [importantly], unlike previous screening trials, this [study] would need to be more representative of the diversity we see in the world,” Haiman concluded. “No population should get left behind.”

References

1. 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(65-75). doi:10.1038/s41588-020-00748-0
2. Largest, most diverse prostate cancer study shows genetic role in health disparities. News release. Keck School of Medicine of the University of Southern California. January 2, 2021. Accessed January 5, 2020. http://bit.ly/3pYhKMN
3. Prostate at a glance. American Cancer Society Cancer Statistics Center. Accessed January 5, 2021. http://bit.ly/3hTbiUs