SNP Linked to Gleason Score 7 Disease Aggression

Genetic variant may help stratify prostate cancer aggression in men with Gleason Score 7 disease

medwireNews: Screening for a variant Allele located near the gene encoding prostate-specific Antigen (PSA) could help predict the presence of aggressive disease in men with Gleason Score (GS)7 prostate cancer, scientists suggest.

As reported in Clinical Cancer Research, 1827 White men with prostate adenocarcinoma were screened for 72 prostate cancer susceptibility genes previously identified in a genome-wide association study.

Three single nucleotide polymorphisms (SNPs) - rs2735839, rs10486567 and rs103294 - significantly predicted highly aggressive prostate cancer, defined as GS8 or above, report Xifeng Wu and co-authors, from the University of Texas MD Anderson Cancer Center in Houston, USA.

Two of these SNPs – rs2735839 and rs10486567 - were also significantly associated with prostate cancer aggression when using the D’Amico low-risk and high-risk classifications, based on PSA, Gleason grade and T stage.

And among the 921 men with biopsy-proven GS7 tumours, the variant allele A at rs2735839 was significantly more common in patients with the less favourable GS4+3 subtype than those with GS3+4 disease.

Multivariate analysis confirmed that men with GS7 prostate cancer who carried the variant A allele of rs27358939 were 1.85 times more likely to have GS4+3 tumours than men without the variant allele, after adjusting for age, PSA and clinical T stage.

Rs2735839 is located 600 base pairs from KLK3 and has previously been shown to influence PSA levels, “providing strong biologic plausibility for its association with prostate cancer aggressiveness”, Xifeng Wu et al say.

“Although the effect size of this single SNP is not sufficient to make such a clinical decision about whether or not treat patients with aggressive therapy, the incorporation of the SNP, together with additional genetic information and other prognostic factors, into a comprehensive nomogram, may affect clinical practice in patients, particularly in patients with clinically defined intermediate risks (e.g., GS 7 diseases), a group for which current clinical decision making is particularly challenging and suboptimal”, the authors write.

They therefore conclude: “Future work is warranted to identify additional genetic loci that can stratify GS 7 patients and test whether these genetic loci can predict prognosis of patients and help personalized clinical management of patients with intermediate-risk profiles.”


He Y, Gu J, Strom S, et al. The prostate cancer susceptibility variant rs2735839 near KLK3 gene is associated with aggressive prostate cancer and can stratify Gleason score 7 patients. Clin Cancer Res 2014; 20: 5133–5139.  doi: 10.1158/1078-0432.CCR-14-0661

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