Gene Points to Aggressive Gleason 7 Prostate Cancer

Xifeng Wu, MD, PhD

A biomarker has been found that may help determine which Gleason 7 (GS7) cancers are particularly aggressive, according to a study published this fall.

Researchers at the University of Texas MD Anderson Cancer Center found that some properties of the KLK3 gene are associated specifically with Gleason 7 prostate cancer, and also with disease aggressiveness, according to a press release issued by the institution.

Found on chromosome 19, KLK3 encodes prostate-specific antigen and is tied to prostate cancer aggression. Further, a particular single nucleotide polymorphism (SNP) on the gene is more apparent in patients who have Gleason 7 prostate cancer, the investigators found.

Of all prostate cancers, 30% to 40% are classified as Gleason 7, an intermediate grade of disease, according to the press release.

In the study, researchers looked at 72 SNPs that had been identified in genome-wide association studies of 1827 prostate cancer patients. They analyzed whether the SNPs were associated with disease aggression by comparing them in aggressive and non-aggressive cases of prostate cancer.

Using a multivariate logistic regression analysis, the investigators determined that patients who carried the risk allele of one SNP in question—the A allele at rs2735839—exhibited a 1.85-fold increased risk of having prostate cancer categorized as the more aggressive Gleason score 4 + 3, as opposed to Gleason score 3 + 4.

“Treatment options for GS7 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 at the cancer center and the study’s lead investigator, in the press release. “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.”

Reference

He Y, Gu J, Strom S, Logothetis CJ, Kim J, Wu X. 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(19):5133-5139.