New Study Shows Viability of Using Ancestry to Compare Prostate Cancer Risk Across Populations

Ancestry has been shown to be a risk factor for prostate cancer. Unfortunately, we know very little about why men of certain races and ethnicities are more prone to get it, let alone how to use genetic information about ancestry to stratify risk across different populations. But according to a new report, a genetic risk score based on a multi-ancestry meta-analysis can stratify men by their risk of developing prostate cancer. The Diagnostic Challenge Black men in the U.S., and other men of African ancestry, are diagnosed with prostate cancer more than men of other races. By the same token, prostate cancer occurs less often in Asian-American and Hispanic/Latino men than in non-Hispanic whites. Ancestry affects not just susceptibility but the age a man is likely to get prostate cancer and whether he is likely to die from it. However, the reasons for these ancestry-based variants remains a mystery. New Genetic Clues Genome analysis may hold the key to unraveling this mystery. There are currently a total of 183 known genetic risk variants for prostate cancer. On Jan. 4, Nature Genetics reported that an international team of researchers had uncovered 86 more. According to the report, the team did this by performing a meta-analysis of genome-wide association studies of prostate cancer that included multiple ancestry populations. Specifically, they analyzed 107,247 prostate cancer cases and 127,006 controls from about a dozen cohorts, including: Ancestries Included in Meta-Analysis

Populations	Cases	Controls
European	85,554	91,972
African	10,368	10,986
East Asian	8,611	18,809
Hispanic	2,714	5,239

The Findings Combining the known 183 with the 86 they discovered, the researched used the 269 risk variants to create genetic risk scores (GRS) for prostate cancer, which they weighted based on ancestry effects. They then compared the risks of developing prostate cancer in men in the top 10 percent of GRS for each ancestry against men with average genetic risk for prostate cancer. Findings:

• Men of European ancestry had five times the risk of developing prostate cancer;
• Men of African ancestry had nearly four times the risk;
• Men of East Asian ancestry had nearly 4.5 times the risk; and
• Hispanic men had about four times the risk.

In addition, they found that the mean GRS of men of African ancestry was slightly more than two times the GRS of men of European ancestry and that men of East Asian ancestry had a mean GRS that was 0.73 times lower than that of men of European ancestry. They also considered the impact of age on the association between GRS and prostate cancer risk, finding that men of European ancestry in the top 10 percent of GRS who are under age 55 had a 6.7 times increased risk, while men of European ancestry above age 55 had a 4.4 times higher risk. Takeaway While the researchers noted that there is no evidence to show that GRS can differentiate risk of aggressive prostate cancer, they also pointed out that roughly half the men with aggressive cancer were in the top 20 percent of GRS. “Genetic risk scores will soon be available for a number of diseases including prostate cancer,” noted one of the researchers.