The circular diagram displays which nearby gene or genes are connected to new variants linked with PSA levels. Kachuri, L., Hoffmann, T.J., Jiang, Y. et al.,Nature Medicine.
Prostate-specific antigen (PSA) screening has long been the gold standard for detecting prostate cancer at an early stage, aiming to improve treatment outcomes and increase survival rates.
But the screening tool is not without its controversies. PSA levels can be affected by various factors, resulting in false positives or negatives. This test may miss some cancers while detecting others that might not actually be clinically significant.
Therefore, there has been a growing interest in the field to find ways to enhance its effectiveness.
The answer might lie in every man’s genes.
In the June 1 online issue of Nature Medicine, a team of researchers from the Icahn School of Medicine at Mount Sinai and collaborators revealed that tailoring prostate cancer screening to individuals, in which PSA is adjusted for genetic factors, could offer a more viable approach to enhancing screening.
“While utilizing blood PSA levels for prostate cancer screening remains contentious due to issues like detecting cancer in men with low PSA and missing it in those with slightly elevated PSA, our multicenter study aimed to improve this approach by accounting for individual genetic variations in PSA levels,” says Robert J. Klein, PhD, Professor, Genetics and Genomic Sciences and a co-author of the paper.
Drawing from Dr. Klein’s earlier research highlighting the impact of individual genetics on PSA levels, this study aimed to determine whether adjusting for these genetic factors could enhance the accuracy of the screening tool.
“The goal is for this to pave the way for using genetically tailored PSA levels for prostate cancer screening, instead of using raw PSA levels,” says Robert J. Klein, PhD.
Using data from several cohorts of healthy men of diverse ancestries, the researchers measured PSA and genetic variants. Computational analyses linked each variant to PSA levels, and an algorithm constructed a genetic model for predicting PSA levels. The study assessed the effectiveness of PSA, either adjusted or not adjusted using this score, in predicting prostate cancer presence upon biopsy.
The researchers found that the score could predict nearly 10 percent of variation in PSA levels. However, it demonstrated more effectiveness in men of European descent than of East Asian or African heritage. Upon applying their scoring method to a dataset comprising men with and without confirmed prostate cancer through biopsy, the researchers estimated that about 30 percent of the men could have been spared from undergoing unnecessary biopsies.
“Our study shows how genetic variants can predict PSA levels and explores using this prediction in patient care. The goal is for this to pave the way for using genetically tailored PSA levels for prostate cancer screening, instead of using raw PSA levels,” says Dr. Klein.
Next, the researchers plan to perform a broader analysis involving more individuals of diverse ancestries, including through the BioMe® biobank at Mount Sinai. This step aims to confirm the applicability of the score across different populations.
Dr. Klein and his team are also exploring, as part of a separate undertaking, whether genetics could be used to better predict individuals at risk for prostate cancers that are potentially life-threatening.