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Polygenic scores identify those at high cancer risk

Apr. 23, 2020, 10:04 AM


by Tom Wilemon

A team of Vanderbilt researchers constructed polygenic risk scores (PRS) based on genomic variants associated with eight common cancers and concluded they could potentially be used for personalized risk assessments.

The study, published recently in JNCI Cancer Spectrum, found that 40.4% of study participants can be classified as having an over twofold elevated risk for at least one site-specific cancer.

In designing the PRS, the researchers used genome-wide association studies data gathered from 400,812 participants of European descent in the UK Biobank. They evaluated the utility of PRS in predicting risk in cancers of the prostate, breast, pancreas, colon/rectum, kidney, bladder, lung and ovary, which collectively account for 59% of new cancer diagnoses in the U.S.

One important study finding is that PRS have the potential to identify people who should start screenings for breast cancer and colorectal cancer before 50, the age recommended by the U.S. Preventive Services Task Force (USPSTF), said senior author Wei Zheng, MD, PhD, director of the Vanderbilt Epidemiology Center and Anne Potter Wilson Professor of Medicine.

“The USPSTF recommendations are for average risk individuals in the general U.S. population,” Zheng said.

“Based on PRS information, some people need to start screenings at an earlier age compared to the general population because their risk of cancer reaches the risk threshold for screening average people would typically reach at age 50 years.”

Overall, 5.7% of the study participants were at a greater than threefold risk for at least one of the eight common cancers. Over the past 10 years, many cancer genes have been identified, and they now are included in clinical genetic testing.

People carrying disease-causing mutations of these genes are at a threefold elevated risk of developing cancer. However, these mutations are quite rare in the general population.

“This means that many people in the general population are at high risk of getting cancer,” Zheng said. “These genetic risk scores can identify a larger number of high-risk people than genes currently included in genetic testing.”

The research team is now looking for opportunities to expand the analysis of PRS for predicting cancer risks, particularly with cohorts that offer more population diversity.

“This paper provides strong support for clinicians and for policymakers to think about using polygenic risk scores for cancer risk assessments,” Zheng said.

The study is the first large prospective study to systematically evaluate the performance of PRS for multiple major cancers.

The study’s leady author is Guochong Jia, MPH. Other contributors include representatives of the Division of Epidemiology, Vanderbilt-Ingram Cancer Center, the Department of Biostatistics, the Vanderbilt Genetics Institute and the Department of Biomedical Informatics.

The research was supported by National Institutes of Health grants (R01CA202981 and R01CA235553) and the Anne Potter Wilson chair endowment at Vanderbilt University.

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