12 Jun PSA Screening For Prostate Cancer Can Be Improved: Genetics May Help
MedicalResearch.com Interview with:
Dr. Graff
Rebecca E. Graff, ScD
Assistant Professor
University of California, San Francisco
Department of Epidemiology & Biostatistics
Mission Hall: Global Health & Clinical Sciences Building
San Francisco, CA 94158
MedicalResearch.com: What is the background for this study?
Response: PSA screening for prostate cancer has long been controversial. While it does seem to reduce mortality attributable to prostate cancer, it also results in the diagnosis of many cancers that never otherwise would have presented symptomatically. In addition, PSA levels are affected by factors other than prostate tumors (e.g., age, prostatic inflammation, and genetics), such that men with high PSA values are often referred for biopsy but do not end up having cancer. We hypothesized that accounting for the genetic component of PSA could yield adjusted values that better distinguish who should get a prostate biopsy.
MedicalResearch.com: What are the main findings?
Response: We identified 128 variants across the genome that are associated with PSA levels, including 82 that had not previously been identified. We also created a genome-wide genetic score that accounted for nearly 10% of variation in PSA levels. Upon using the score to adjust raw PSA values in a population comprised of biopsied men with and without prostate cancer, we found that ~30% of the population could have been spared a biopsy. The adjusted PSA values were especially valuable for improving detection aggressive disease.
MedicalResearch.com: Can this model be readily adapted for wider user?
Response: The model is not quite ready for widespread implementation. The adjusted PSA levels would have missed roughly 9% of positive biopsies, though most were non-aggressive tumors. The model also does a better job improving PSA screening in men of European ancestry than in men of other ancestries. Equitable screening will require a score that works well in diverse populations – something that we are currently working to develop. Once there exists a score that has been well validated, the genetic adjustment approach is definitely scalable.
MedicalResearch.com: What should readers take away from your report?
Response: Readers should take away that PSA screening can be better than it currently is. Understanding the genetic factors that affect PSA levels in the absence of prostate cancer can help us reduce the “noise” in the measure.
MedicalResearch.com: What recommendations do you have for future research as a results of this study?
Response: Future research should focus on improving PSA screening in diverse ancestral populations.
Disclosures: This study was funded by the National Cancer Institute (R01CA241410). John S. Witte, PhD, principal investigator on the study, is a non-employee cofounder of Avail Bio.
Citation:
Kachuri, L., Hoffmann, T.J., Jiang, Y. et al. Genetically adjusted PSA levels for prostate cancer screening. Nat Med (2023). https://doi.org/10.1038/s41591-023-02277-9
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