NEW YORK (Reuters Health) - Researchers at The University of Texas MD Anderson Cancer Center have identified a genetic variant that can help predict which patients with Gleason score 7 (GS7) prostate cancer will have a more aggressive form of the disease.
The variant resides near the KLK3 gene on chromosome 19, which encodes the prostate-specific antigen (PSA). The new findings hint that this gene is not only associated with prostate cancer aggressiveness, but a single nucleotide polymorphism (SNP) on it is more apparent in patients with GS7 disease, the investigators say.
GS7 prostate cancer is an intermediate grade of cancer accounting for 30% to 40% of all prostate cancers. "Patients with GS7 prostate cancer are a heterogeneous group with dramatically different prognosis and currently there are no reliable biomarkers to further stratify this group," the authors note in a report in Clinical Cancer Research October 1.
The researchers genotyped 72 SNPs identified from the genome-wide association studies (GWAS) in 1,827 prostate cancer patients. They analyzed associations of these SNPs with aggressiveness of the cancer, comparing them in clinically defined cases of high-aggressive (GS ≥ 8) and low-aggressive (GS ≤ 6) prostate cancer.
They found that three SNPs - rs2735839, rs10486567, and rs103294 - were associated with biopsy-proven high-aggressive (GS ≥ 8) prostate cancer (p<0 .05="" p="">
They also found that the frequency of the variant allele (A) at rs2735839 was significantly higher in patients with biopsy-proven GS 4 + 3 disease than in those with GS 3 + 4 disease (p=0.003). The GS 4 + 3 subtype has had less favorable clinical outcomes than the GS 3 + 4 subytpe, the authors note.
In multivariate analysis, patients with the A allele at rs2735839 had a 1.85-fold increased risk of being GS 4 + 3 relative to those with GS 3 + 4.
The authors note that the rs2735839 SNP sits 600 base pair downstream of the KLK3 gene on chromosome 19 "and has been shown to modulate PSA level, providing strong biologic plausibility for its association with prostate cancer aggressiveness."
In this study, "We confirmed an association of the rs2735839 with high-aggressive prostate cancer (GS ≥ 8). Moreover, we reported for the first time that rs2735839 can stratify GS 7 patients, which would be clinically important for more accurately assessing the clinical behavior of the intermediate-grade prostate cancer and for tailoring personalized treatment and posttreatment management," the write in their paper.
Senior author Dr. Xifeng Wu added in a statement, "Treatment options for the GS7 disease are controversial because the burden of combined treatment modalities may outweigh the potential benefit in some patients. It is critical that we develop personalized treatments based on additional biomarkers to stratify GS7 prostate cancers. Additional biomarkers may help us achieve personalized clinical management of low and intermediate risk prostate cancer patients."
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 authors did not respond to request for comment by press time.
SOURCE: http://bit.ly/1xpryhN
Clin Cancer Res 2014;20:5133-5139.
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