Researchers Discover Genetic Variant That Can Predict Aggressive Prostate Cancer at Diagnosis
Researchers at The University of Texas MD Anderson Cancer Center have identified a biomarker adjacent to the KLK3 gene that can predict which prostate cancer patients with a Gleason score of 7 will have a more aggressive form of cancer. The findings by He et al, published in Clinical Cancer Research, indicate that the KLK3 gene—a gene on chromosome 19 responsible for encoding the prostate-specific antigen (PSA)—is not only associated with prostate cancer aggression, but a single nucleotide polymorphism (SNP) on it is more apparent in patients with a Gleason score of 7.
Researchers have linked Gleason score, an important predictor of prostate cancer outcomes, to several clinical endpoints, including clinical stage, cancer aggression, and survival. There has been much research associated with prostate cancer outcomes as well as prostate cancers with a Gleason score of 7, an intermediate grade of cancer accounting for 30% to 40% of all prostate cancers.
“This is the first report that I am aware of that indicates a genetic variant can stratify [Gleason score 7] prostate cancer patients,” said Jian Gu, PhD, Associate Professor at MD Anderson, and a key investigator on the study. “This is important because this group with heterogeneous prognosis is difficult to predict and there are no reliable biomarkers to stratify this group.”
Study Details
In this study, researchers investigated inherited genetic variants to see if there would be any promising biomarkers for prostate cancer patients. The investigators studied the genetic makeup of 72 SNPs identified from the genome-wide association studies in 1,827 prostate cancer patients. They analyzed associations of these SNPs with disease aggression, comparing them in clinically defined high and low aggressive cases. They found a SNP on the KLK3 gene, rs2735839, that can predict an aggressive form of Gleason score 7 disease.
“Treatment options for the [Gleason score 7] disease are controversial because the burden of combined treatment modalities may outweigh the potential benefit in some patients,” said Xifeng Wu, MD, PhD, Professor and Chair of Epidemiology, and lead investigator on the study. “It is critical that we develop personalized treatments based on additional biomarkers to stratify [Gleason score 7] prostate cancers. Additional biomarkers may help us achieve personalized clinical management of low and intermediate risk prostate cancer patients.”
Dr. Wu also said her team are expanding the study and taking a pathway-based approach to systemically investigate genetic variants in microRNA regulatory pathways as biomarkers for the prognosis of prostate cancer patients. “We are also working on circulating biomarkers. Eventually, we will incorporate all biomarkers, epidemiological and clinical variants into nomograms to best predict the prognosis of prostate cancer patients at diagnosis.”
Dr. Wu is the corresponding author for the Clinical Cancer Research article.
The study was funded by the National Cancer Institute and MD Anderson Cancer Center institutional support for the Prostate Cancer Moon Shots Program and the Center for Translational and Public Health Genomics.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
