Newly Discovered Genetic Variants Tied to Prostate Cancer

A multi-ancestry genome-wide association study (GWAS) has revealed more than 180 novel genetic variants associated with prostate cancer.

Incorporating these variants into genetic risk scores (GRS) may improve their effectiveness, according to researchers. They reported their findings in Nature Genetics.

In this GWAS, the researchers evaluated 156,319 prostate cancer patients and 788,443 control individuals of European, African, Asian, or Hispanic descent. The researchers noted that the case sample had more African, Asian, and Hispanic patients than previous multi-ancestry GWAS analyses.

The researchers identified 451 independent risk variants for prostate cancer that were genome-wide significant, including 187 variants that were previously unreported.

“The underlying rationale for conducting a cross-ancestry meta-analysis is based on the hypothesis that true causal variants are predominantly shared across populations,” the researchers noted.

Of the 451 variants identified, 75% in European, 10% in African, 9% in Asian, and 2% in Hispanic populations were significant genome-wide. However, some of these were population-specific, with a minor allele frequency of 1% or less in the other populations.

The researchers also compared the performance of GRS using past marker sets (GRS₁₀₀, GRS₁₈₁, and GRS₂₆₉) and the current set of 451 variants (GRS₄₅₁.)

The researchers noted that, with GRS₄₅₁, there was greater stability when assigning unaffected patients to GRS categories. With GRS₁₀₀ and GRS₁₈₁, 58% of men in the lowest or highest quintile remained in the same category. However, between GRS₂₆₉ and GRS₄₅₁, 69% to 70% remained in the same risk category.

“Likewise, the percentage of cases has increased for each population within higher GRS categories (for example, from 40.5% in the highest quintile of GRS₁₀₀ to 51.2% in GRS₄₅₁) and decreased within lower GRS categories (for example, from 7.5% in the lowest quintile of GRS₁₀₀ to 4.4% in GRS₄₅₁),” the researchers explained.

The improvement in risk classification with GRS₄₅₁ was confirmed in replication studies including patients of European and African descent who were not included in the GWAS data used for this analysis, according to the researchers.

The team also found that, in prostate cancer patients of African ancestry, GRS₄₅₁ was associated with an increased risk of aggressive disease (odds ratio per standard deviation, 1.08; 95% CI, 1.04-1.12; P =1.1 × 10^-4).

“While GRS for prostate cancer is a highly effective tool for risk stratification and personalized risk assessment, how and when this information should be included in the decision-making process for prostate cancer screening and early detection need to be determined,” the researchers concluded.

Disclosures: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Wang A, Shen J, Rodriquez AA, et al. Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants. Nat Genet. Published online November 9, 2023. doi:10.1038/s41588-023-01534-4

This article originally appeared on Cancer Therapy Advisor