Five genetic variants may help identify lethal prostate Ca

An international team of researchers has identified five inherited genetic variants that are strongly associated with aggressive, lethal prostate cancer.

The discovery ultimately could lead to the development of a simple blood test that could be given upon diagnosis to determine which men should receive aggressive treatment versus a more conservative approach.

"Biomarkers that could distinguish between patients with indolent versus more aggressive tumors are urgently needed," said senior author Janet L. Stanford, PhD, of Fred Hutchinson Cancer Research Center, Seattle. "The panel of markers we’ve identified provides the first validated evidence that inherited genetic variants play a role in prostate cancer progression and mortality. Ultimately, these markers could be used in the clinic, along with other known predictors that are used to assess tumor aggressiveness, to identify men with a high-risk profile."

The panel of five single-nucleotide polymorphisms (SNPs) consists of LEPR, RNASEL, IL4, CRY1, and ARVCF.

"We chose to study SNPs in genes that potentially play a key role in biological pathways that may contribute to prostate cancer progression such as inflammation, steroid-hormone production and metabolism, DNA repair, circadian rhythm, and vitamin D activity," Dr. Stanford said.

For the study, which was published online in Cancer Epidemiology, Biomarkers and Prevention (Aug. 17, 2011), the authors analyzed DNA in blood samples taken from a population-based group of 1,309 Seattle-area prostate cancer patients aged 35 to 74 years at the time of diagnosis. They evaluated 937 SNPs in 156 candidate genes and, of these, 22 SNPs emerged as being significantly associated with prostate cancer-specific mortality.

A subsequent validation study of these 22 SNPs was conducted in another population-based group of 2,875 prostate cancer patients in Sweden who were age 35 to 74 at diagnosis. Upon genotyping DNA from their blood, five of the 22 SNPs emerged as being significantly associated with death from prostate cancer. A higher proportion of patients from Sweden (17.4%) had died of prostate cancer relative to those from Seattle (4.6%) during a median follow-up period of 6.5 years.

Patients who carried four or all five of these genetic markers had a 50% higher risk of dying from their prostate cancer than patients who had two or less. The risk of dying from prostate cancer increased with the number of SNP genetic variants a patient carried.

"While previous studies have suggested that genetic background influences prostate cancer outcomes, this is the first study to validate genetic markers associated with lethal disease," Dr. Stanford said.