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Study compiles probably the most comprehensive list of genetic variants related to prostate cancer risk

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Study compiles probably the most comprehensive list of genetic variants related to prostate cancer risk

A globe-spanning scientific team has compiled probably the most comprehensive list of genetic variants related to prostate cancer risk -; 451 in all -; through a whole-genome evaluation that ranks as the most important and most diverse investigation into prostate cancer genetics yet. The research, led by the USC Center for Genetic Epidemiology, the Keck School of Medicine of USC and USC Norris Comprehensive Cancer Center, and in the UK by The Institute of Cancer Research, London, included major increases in representation amongst men from racial and ethnic groups which have often been overlooked of such research, revising what is understood about genetic risk for the disease.

With these findings, the researchers improved a system they developed for measuring genetic risk in order that it was more practical in predicting who would or would not develop prostate cancer -; even distinguishing between the likelihood of aggressive and less-serious cases amongst men of African descent. The finding that higher risk scores based on the 451 variants correlated with more-aggressive disease in men of African ancestry is a meaningful step toward improving early detection and making higher informed decisions about screening.

The study, published in Nature Genetics, builds on 2021 research documented in the identical journal that found 269 genetic variants correlating with prostate cancer risk, based on a sample of nearly 235,000 men. The brand new results were derived from genomic information from near 950,000 men.

We’re not going to learn all the pieces there may be to know concerning the genetics of prostate cancer by studying only white men. Larger and bigger studies, engaging a broader spectrum of populations, are vital if we will discover genetic markers of risk and develop risk prediction tools which are equally effective across populations.”

Christopher Haiman, ScD, co-senior writer, holder of the AFLAC Chair in Cancer Research and professor of population and public health sciences on the Keck School of Medicine

A considerable revision of what is known about genetic risk for prostate cancer

The researchers compared genomic data from 156,319 prostate cancer patients with that of a control group totaling 788,443. From the previous study, there was an 87% increase within the variety of prostate cancer cases included from men of African ancestry, 45% from Latino ethnicity, 43% from European ancestry and 26% from Asian ancestry.

Haiman and his colleagues found 187 recent genetic variants related to prostate cancer risk. In addition they found 150 genetic variants from earlier research that were replaced by variants in nearby spots on the DNA double helix that higher correlated with prostate cancer risk through the lens of the larger, more diverse sample.

“It’s a crucial refinement to seek out markers which are higher at capturing risk across populations,” said Haiman, who can be director of the USC Center for Genetic Epidemiology and co-leader of the Cancer Epidemiology Program at USC Norris cancer center. “The thought of precision medicine and global medicine for all depend on including and integrating information across populations, because one of the best marker determined in whites won’t be one of the best marker overall.”

Progress in assessing risk because of a global effort

Along with fueling further research, the outcomes have the potential to learn human health by providing men with personalized risk information that they’ll use when having discussions with their doctors about screening and treatment. Ultimately the research could lay the bottom work for genetic testing to discover those at greater risk for aggressive prostate cancer and enable early detection by screening them earlier and more often.

Because many prostate cancer cases diagnosed today might never reach the purpose where they’re life-threatening -; resulting in unnecessary treatment that may degrade quality of life -; differentiating between risk for aggressive disease is vital. Up until now, the scientists’ system for calculating risk scores has correlated with likelihood of developing prostate cancer, but lacked predictive value about how serious a given case could also be.

“We’ll proceed to enhance this risk rating, and search for markers that help to tell apart aggressive from less aggressive disease,” Haiman said. “Clinical trials can be required to judge the effectiveness of the chance rating in helping doctors and patients make decisions about screening.”

This research combined the information from virtually every study thus far examining DNA for genetic variants related to prostate cancer risk. The U.S. Veterans Health Administration’s Million Veteran Program and Argonne National Laboratory proved to be essential partners [for including diverse populations in the study]. Bringing all of it together required a team effort encompassing greater than 300 researchers from well over 100 institutions, in 26 nations -; from Barbados to Bulgaria, Nigeria to the Netherlands and Japan to Ghana.

“This shows what happens when the world research community comes together to make improvements for all,” Haiman said. “The undeniable fact that everyone was so willing to collaborate was enormously critical.”

About this study

The primary writer of the study is Anqi Wang, who earned her doctorate from the Keck School of Medicine in 2023. David Conti, professor of population and public health sciences on the Keck School and associate director of information science integration at USC Norris cancer center, was co-senior writer. Amongst a whole lot of co-authors, other study collaborators related to the Keck School are Jiayi Shen, Fei Chen, Xin Sheng, Yili Xu, Alisha Chou, Ali Sahimi, Peggy Wan, Sue Ingles, Mariana Stern, Roberta McKean-Cowdin, Zeyun Lu and Nick Mancuso.

This study was supported by the National Institutes of Health (R01CA257328, U19CA214253, U01CA261339, P01CA196569, R00CA246063) and the Prostate Cancer Foundation (20CHAS03, 21YOUN11).

Source:

Journal reference:

Wang, A., et al. (2023). Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants. Nature Genetics. doi.org/10.1038/s41588-023-01534-4.

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