Researchers in Seattle and Sweden have identified five inherited genetic markers associated with aggressive, lethal prostate cancer.
The finding that could lead to the development of a simple blood test that could help determine who should receive aggressive treatment and who could opt for more conservative approaches.
“Biomarkers that could distinguish between patients with indolent versus more-aggressive tumours are urgently needed,” said Janet L. Stanford, Ph.D., co-director of the Fred Hutchinson Cancer Research Center Program.
“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, such as a high Gleason score, to identify men with a high-risk profile,” she added.
For the study, the researchers analyzed DNA in blood samples taken from a population-based group of 1,309 Seattle-area prostate cancer patients who were age 35 to 74 at the time of diagnosis.
A subsequent validation study of these 22 single-nucleotide polymorphisms, or SNPs (pronounced “snips”) 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.
The five SNPs were located in or tagged, one each, to five genes that may affect prostate cancer progression:
LEPR – The strongest marker associated with prostate cancer mortality in the study was the leptin receptor gene, which helps control tissue growth, inflammation, blood-vessel development and bone density. The latter effect makes LEPR an interesting candidate for understanding disease progression, since the primary metastatic site for prostate cancer is bone, and such metastases are predictive of fatal disease.
RNASEL – This gene is associated with hereditary prostate cancer and is associated with apoptosis (programmed cell death), inflammation and the ability of cells to proliferate and stick to each other (hallmarks of cancer growth).
IL4 – This Interleukin 4 gene is associated with tumor growth, blood vessel development and cancer cell migration.
CRY1 – Cytochrome 1 is a gene that impacts the circadian rhythm and thereby may affect androgen levels, which are known to be involved in prostate cancer progression.
ARVCF – This gene is a member of the catenin family of proteins, which help the inside and outside of cells “talk” to each other. Increased expression of ARVCF has been shown to disrupt cell adhesion, which may facilitate cancer progression.
Patients who carried four or all five of these genetic markers had a 50 percent higher risk of dying from their prostate cancer than patients who had two or fewer. 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,” said Stanford.
The study has been published online ahead of the September issue of Cancer Epidemiology, Biomarkers and Prevention.