New genetic risk factors for prostate cancer identified in men of African ancestry
Key takeaways:
- The nine risk factors include seven found predominantly or exclusively among men of African ancestry.
- A polygenic risk score differentiated between aggressive vs. nonaggressive disease.
A genome-wide association study of more than 80,000 men with prostate cancer identified nine new genetic risk factors for prostate cancer, including seven mainly or exclusively among men of African ancestry.
The results, published in European Urology, additionally showed the effectiveness of a polygenic risk score in stratifying prostate cancer risk and differentiating between risk for aggressive vs. nonaggressive disease.
Rationale and methodology
“The ability to differentiate between the risk for aggressive and nonaggressive forms of [prostate cancer] is of critical importance,” Christopher Haiman, ScD, AFLAC chair in cancer research at USC Norris Comprehensive Cancer Center, said in a press release. “Until now, risk scores haven’t been able to do that.”
Researchers conducted a meta-analysis of 10 genome-wide association studies including 19,378 cases and 61,620 controls of African ancestry. Researchers sought to identify common genetic variants contributing to risk for prostate cancer. They tested genotyped and imputed variants for their association with prostate cancer risk, identified novel susceptibility loci and incorporated them into a multiancestry polygenic risk score. Researchers then evaluated the score for associations between prostate cancer risk and disease aggressiveness.
Findings
Researchers identified nine novel susceptibility loci for prostate cancer.
Among them, seven appeared significantly more common among men of African ancestry, including an African-specific stop-gain variant in the prostate-specific gene anoctamin 7 (ANO7).
Results also showed a multiancestry polygenic risk score that included 278 risk variants identified significant associations of prostate cancer risk in studies of men of African ancestry (ORs > 3 for men in the top polygenic risk score decile and ORs > 5 for men in the top polygenic risk score percentile).
Moreover, men in the top polygenic risk score decile experienced significantly higher risk for aggressive prostate cancer than men in the 40% to 60% polygenic risk score category (OR = 1.23; 95% CI, 1.1-1.38).
Implications
“Prostate cancer survival is significantly lower among men diagnosed with aggressive disease,” Fei Chen, PhD, assistant professor in the department of clinical population and public health sciences at Keck School of Medicine of USC, said in the press release. “Our findings suggest that these polygenic risk scores could be useful for identifying men who may benefit from earlier and more frequent screenings.”
References:
- Chen F, et al. Eur Urol. 2023;doi:10.1016/j.eururo.2023.01.022.
- Largest-ever genetic study of prostate cancer in men of African descent finds new risk factors for the disease (press release). Available at: medicalxpress.com/news/2023-03-largest-ever-genetic-prostate-cancer-men.html. Published March 3, 2023. Accessed March 20, 2023.
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