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Some racial and ethnic groups suffer relatively more often, and fare less well, from common illnesses than others. Prostate cancer is a disease where such health disparities occur: the risk of the disease is about 75% higher, and prostate cancer is more than twice as deadly in blacks as in whites. Yet whites are often overrepresented as research participants, making these differences difficult to understand and, ultimately, to resolve.
With this problem in mind, scientists at the USC Center for Genetic Epidemiology and the Institute for Cancer Research in London conducted a study that brings together data from the majority of studies on genomic prostate cancer around the world. Including more than 200,000 men of European, African, Asian and Hispanic descent from around the world, the study is the largest and most diverse genetic analysis ever performed for prostate cancer – and possibly for all. other cancer.
The paper appears today in Genetics of nature.
The study’s authors identified 86 new genetic variations that increase prostate cancer risk, not previously discovered, bringing the total number of prostate cancer risk loci to 269. Applying a model to assess Prostate cancer risk based on the interaction of these genetic factors, the researchers showed that men of African descent on average inherit about twice the risk of prostate cancer compared to men from European ancestry, while men of Asian descent inherit about three-quarters of the risk from their white counterparts – evidence that genetics play a role in the differences in how often cancer occurs in different racial groups.
This research is also a step towards the application of precision medicine to early detection.
“Our long-term goal is to develop a genetic risk score that can be used to determine a man’s risk of developing prostate cancer,” said corresponding author Christopher Haiman, ScD, professor of preventive medicine at USC’s Keck School of Medicine and director of the USC Center for Genetic Epidemiology. “Men at higher risk may benefit from earlier and more frequent screening, so the disease can be identified when it is more treatable.”
Study tackles health disparities
Praise for the study’s potential to increase health equity came from Jonathan W. Simons, MD, president and CEO of the Prostate Cancer Foundation. The foundation is funding Haiman’s further work as the head of the RESPOND initiative exploring disease in African American men.
“PCF believes that Dr. Haiman’s research results will lead to more effective precision prostate cancer screening strategies for men of West African descent,” said Simons. “PCF is convinced that identifying these very high risk individuals will have a positive impact on this significant disparity in healthcare.
Haiman and his colleagues used genomic data sets from countries like the US, UK, Sweden, Japan, and Ghana to compare 107,247 men with prostate cancer to a control group including 127,006 men. By looking at a spectrum of races and ethnicities, the study authors aim to make the genetic risk score more useful for more people.
“We not only found new markers of risk, but also demonstrated that by combining genetic information between populations, we were able to identify a risk profile that can be applied to all populations,” Haiman said. “This underscores the value of adding multiple racial and ethnic populations in genetic studies.”
Risk score could contribute to better screening
Current prostate cancer screening guidelines suggest that people 55 years and older at average risk may choose to have prostate specific antigen (PSA) testing in consultation with their doctor. High levels of PSA are associated with prostate cancer, but the PSA test tends to detect slow growing tumors. With widespread use, this too often leads to unnecessary treatment.
The value of the PSA test as a screening tool would increase if it were selectively deployed to monitor people at high risk for prostate cancer – where the genetic risk score might come into play. particularly high could even start screening before the age of 55.
In order to translate the results of current research into better early detection, a large-scale clinical trial would be needed.
“Most importantly, unlike previous screening trials, this one should be more representative of the diversity we see around the world,” Haiman said. “No population should be left behind.”
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About this study
The article has over 230 co-authors, representing dozens of organizations. The co-first authors of the study are David Conti, PhD, professor of preventive medicine, and Burcu Darst, PhD, postdoctoral researcher and research associate, both of the Keck School of Medicine. Co-lead authors are Haiman, on behalf of the Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE) consortium, and Rosalind Eeles, FMedSci, PhD, FRCP, FRCR, and Zsofia Kote-Jarai, PhD, on behalf of the Prostate. Cancer Association Group to Investigate Cancer Associated Alterations in the Genome Consortium (PRACTICAL).
This study was supported by the National Institutes of Health (U19CA148537, R01CA194393, K99CA246063), with additional support from Cancer Research UK, Prostate Cancer UK and the Movember Foundation.
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