Genetic Link to Aggressive Prostate Cancer Identified

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Soon it may be possible to determine whether a newly diagnosed prostate tumor is more likely to be indolent or aggressive. Jianfeng Xu, MD, professor of epidemiology and cancer biology, Wake Forest University Baptist Medical Center, North Carolina, and colleagues discovered a genetic variant predictive of aggressive prostate cancer.

“This finding addresses one of the most important clinical questions of prostate cancer—the ability at an early stage to distinguish between aggressive and slow-growing disease,” Xu said. The authors believe that this genetic marker, combined with other currently undetermined variables, may someday guide treatment decisions in clinical practice.

Xu’s team, like researchers at other institutions, have previously identified various genetic factors that suggest an increased risk of developing prostate cancer. This is the first time, however, that scientists have found a marker that helps predict the likely course of a disease.

The investigators analyzed genetic samples from 4849 men with aggressive prostate cancer to look for common genetic variants. They compared the genetic profiles to profiles from 12,205 men with indolent disease. Patient samples were from the National Cancer Institute’s Genetic Markers of Susceptibility study and various US and Swedish studies. In total, 7 patient populations were included in the analyses.

The rs4054823 single nucleotide polymorphism (SNP) at chromosome 17p12 was significantly associated with a 25% greater risk of developing associate disease (P = 2.1 x 10-8). It was not found to be associated with slow-growing disease. “A single variant with a moderate effect such as this is unlikely to be sufficient on its own at predicting risk,” Xu said. “But its identification is significant because it indicates that variants predisposing men to aggressive disease exist in the genome.”

Xu expects that, in the future, investigators will identify other SNPs that help predict aggressive disease, someday allowing physicians to screen men at diagnosis. This could be used to distinguish those who need early treatment while the disease is more likely to be cured and those who are candidates for a watchful waiting approach as outlined in the new National Comprehensive Cancer Network guidelines.

PNAS

Xu J, Zheng SL, Isaacs SD, et al. Inherited genetic variant predisposes to aggressive but not indolent prostate cancer. . 2010. [Epub ahead of print.]