Comprehensive Study Discovers 451 Genetic Markers Linked to Prostate Cancer

In an expansive study that analyzed the genetic data of nearly 950,000 men from various ethnic backgrounds, researchers have discovered 451 genetic variants that are associated with an increased risk of developing prostate cancer. This significant discovery advances the precision and effectiveness of risk prediction and screening processes, particularly benefiting men of African descent.

A global research endeavor spearheaded by USC has delved into the genomes of close to a million men, identifying 451 genetic markers and refining the current understanding of the genetic predispositions to prostate cancer.

A far-reaching team of scientists has developed the most extensive catalog of genetic markers linked to prostate cancer, with 451 identified variants. This achievement stems from the largest and most diverse whole-genome analysis conducted on the subject of prostate cancer genetics to date.

The investigation placed a notable emphasis on including men from racial and ethnic groups that have historically been underrepresented in such studies, thereby revising the comprehension of genetic predispositions to the disease. The study was conducted under the leadership of the USC Center for Genetic Epidemiology, the Keck School of Medicine of USC, and the USC Norris Comprehensive Cancer Center, along with the Institute of Cancer Research in London.

Advancements in Genetic Risk Evaluation

The study’s findings have led to the enhancement of a genetic risk assessment tool previously developed by the researchers. This improved tool now more accurately predicts prostate cancer occurrence, distinguishing between the probabilities of developing either an aggressive or less serious form of the disease among men of African ancestry. The correlation between higher risk scores based on the 451 identified variants and more aggressive forms of prostate cancer in these men represents a substantial advancement in the early detection of the disease and in making more informed screening decisions.

This research, detailed in the November 9th issue of Nature Genetics, builds upon a 2021 study published in the same journal, which identified 269 genetic variants linked to prostate cancer from a sample of nearly 235,000 men. The recent results have been derived from the genetic information of almost 950,000 men.

The Importance of Genetic Diversity in Research

Co-senior author Christopher Haiman, ScD, emphasized the importance of including a diverse array of populations in genetic studies, stating that understanding the genetics of prostate cancer cannot be fully achieved by studying solely white men. He stressed the necessity of larger studies that incorporate a wide range of populations in order to identify genetic risk markers and develop effective risk prediction tools across different demographics.

The study analyzed and compared the genomic data of 156,319 prostate cancer patients with a control group of 788,443 individuals. The new study marked an 87% increase in prostate cancer cases from men of African ancestry and significant increases from other ethnicities compared to the previous study, leading to the identification of 187 new genetic variants linked to prostate cancer risk.

Haiman also noted the importance of refining the markers to better capture risk across different populations, highlighting the concept of precision and global medicine which relies on integrating information from diverse populations.

Progress in Risk Assessment

The outcomes of this study not only propel further research but also offer tangible health benefits by providing personalized risk information for men. Such information can be crucial during discussions with their physicians about screening and treatment options. The findings could pave the way for genetic testing to identify individuals at a higher risk for aggressive prostate cancer, thus enabling more proactive and frequent screenings.

Since many prostate cancer diagnoses today might not pose a life-threatening risk and can lead to unnecessary treatments affecting the quality of life, it is essential to differentiate between the risks of aggressive disease. The risk score system previously used by the scientists correlated with the probability of developing prostate cancer but was not predictive of the disease’s severity.

Continued efforts are aimed at improving the risk score and identifying markers that differentiate aggressive from less aggressive forms of the disease, with clinical trials planned to evaluate the effectiveness of the risk score in assisting medical decisions regarding screening.

International Collaboration and Future Outlook

This research amalgamates data from virtually all DNA studies to date on genetic variants linked to prostate cancer risk. The study benefited from key partnerships with the U.S. Veterans Health Administration’s Million Veteran Program and the Argonne National Laboratory, essential for the study’s diversity. A collaborative team of over 300 researchers from more than 100 institutions across 26 countries contributed to this monumental effort.

Haiman praised the global research community’s willingness to collaborate, which was crucial for the study’s success.

Reference: “Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants” 9 November 2023, Nature Genetics.
DOI: 10.1038/s41588-023-01534-4

Anqi Wang, a recent doctoral graduate from the Keck School of Medicine, is credited as the first author of the study. David Conti, co-senior author alongside other notable contributors, is also recognized for his roles in public health sciences at the Keck School and data science integration at the USC Norris Comprehensive Cancer Center.

The research received support from the National Institutes of Health and the Prostate Cancer Foundation.

Frequently Asked Questions (FAQs) about prostate cancer genetics

More about prostate cancer genetics

• USC Center for Genetic Epidemiology
• Keck School of Medicine of USC
• USC Norris Comprehensive Cancer Center
• The Institute of Cancer Research, London
• Nature Genetics Journal Article
• National Institutes of Health Funding
• Prostate Cancer Foundation