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Genetic Score Predicts Prostate Cancer Risk Across Ancestry Populations

NEW YORK – A genetic risk score based on a multi-ancestry meta-analysis can stratify men by their risk of developing prostate cancer.

Prostate cancer affects some 207,000 men each year in the US, according to the US Centers for Disease Control and Prevention, but African-American men are more likely than white men to develop prostate cancer.

In a meta-analysis of genome-wide association studies of prostate cancer that included multiple ancestry populations, an international team of researchers uncovered 86 new genetic risk loci. By bundling these new loci together with known risk variants, the researchers developed an ancestry-weighted genetic risk score that can stratify prostate cancer risk across populations, as they reported Monday in Nature Genetics.

Knowing someone's risk of disease could help with prevention or screening efforts, co-senior author Christopher Haiman, a professor of preventive medicine at the University of Southern California, said in an email.

For their meta-analysis, the researchers examined 107,247 prostate cancer cases and 127,006 controls from about a dozen cohorts. In particular, the analysis included 85,554 cases and 91,972 controls of European ancestry; 10,368 cases and 10,986 controls of African ancestry; 8,611 cases and 18,809 controls of East Asian ancestry, and 2,714 cases and 5,239 controls from Hispanic populations. 

Through this, they uncovered 86 new, independent genetic loci associated with prostate cancer risk. 

In all, these new variants bring the total of prostate cancer genetic risk variants to 269. In general, these risk variants were equally associated with risk of aggressive disease or with age at prostate cancer diagnosis across ancestry groups. However, the effect estimates differed across ancestry groups.

The researchers combined these 269 risk variants to develop genetic risk scores (GRS) for prostate cancer, which they weighted based on ancestry effects. As compared to men with average genetic risk for prostate cancer, men of European ancestry in the top 10 percent of GRS had five times the risk of developing prostate cancer, while men of African ancestry in the top decile of GRS had nearly four times the risk. Additionally, men of East Asian ancestry in the top 10 percent had about 4.5 times the risk of developing prostate cancer and Hispanic men had about four times the risk. 

At the same time, men of African ancestry had a mean GRS that was slightly more than two times that of men of European ancestry, while men of East Asian ancestry had a mean genetic risk score that was 0.73-times lower than that of men of European ancestry.

Age further modified the association between GRS and prostate cancer risk. Men of European ancestry in the top decile under the age of 55 and had 6.7 times increased risk of prostate cancer, while men of European ancestry older than 55 had 4.4-fold increased risk.

While the researchers noted there is no evidence the GRS can differentiate risk of aggressive prostate cancer, they noted that about half the men with aggressive prostate cancer were in the top 20 percent of GRS. This suggested to them that the scores can uncover men in which aggressive disease is more likely to occur. 

"Genetic risk scores will soon be available for a number of diseases including prostate cancer," Haiman said, adding that "for prostate cancer, it may be helpful to know a man's risk in their 40s so that those at high risk could start PSA screening earlier, with delayed screening for men at very low risk."

Haiman and his colleagues have a number of studies aimed at further developing their risk score in populations of non-European ancestry, including through the Research on Prostate Cancer in African American Men: Defining the Roles of Genetics, Tumor Markers, and Social Stress (RESPOND) study.