Men who have a family history of prostate cancer have a two-fold greater risk of developing the disease. Currently, approximately 100 genetic variants have been found to influence the risk of prostate cancer. However, these variants only account for 33 percent of the increased familial risk, suggesting that additional genetic factors must also exist.
Moffitt researchers participated in a large, international study that is part of the PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) consortium whose goal is to identify genetic risk factors associated with prostate cancer. They compared the genetic information from 22,301 prostate cancer cases and 22,320 normal control cases from 23 different clinical studies. The research team focused their analysis on segments of genetic material called microRNAs.
“MicroRNAs are small molecules that work as ‘master-regulators,’ controlling multiple cancer-related genes by binding regulatory regions of target genes,” explained Jong Park, Ph.D., associate member and molecular epidemiologist in the Cancer Epidemiology Program at Moffitt.
The researchers discovered 22 microRNA binding site variations that influence the risk of developing prostate cancer. Among these 22 variations, 10 of them were not investigated thoroughly as being potential risk factors. Importantly, 7 of the variants could differentiate between aggressive and nonaggressive disease.
The researchers further confirmed the importance of two of these genetic variants by investigating how they influence protein expression in normal and cancerous prostate tissue. They discovered that one of the variants plays an important role in mediating expression of the prostate serum marker PSA, and the second variant controls expression of a gene involved in metabolism.
“The hope is that this research may eventually lead to a simple genotyping based blood test that could be used in conjunction with the PSA and DRE tests to aid the medical team and patient in accurately predicting disease risk,” said Park. The results from this research may also allow physicians to differentiate between slow-growing and aggressive prostate tumors, and aid in therapeutic decisions.
The study was published in the February 17 issue of Cancer Discovery.