A team of Finnish researchers has identified a signature of SNPs associated with genetic predisposition to prostate cancer that could be used to determine which men with benign prostate hyperplasia are at risk of later developing malignant disease.
In a recent study, which the group presented in a poster at the annual European Association of Urology congress in Milan last month, the team identified 10 markers with a statistically significant association to risk of developing prostate cancer for men who currently have BPH.
Leena Saaristo, one of the study authors, told PGx Reporter in an email that the team hopes the results could eventually lead to a test for heightened cancer risk in men who have been diagnosed with BPH. Such a test could help physicians make decisions about targeted screening and more aggressive treatment.
"The BPH patients carrying these high risk alleles are at increased risk of developing prostate cancer [and] for some of the SNPs, the risk ratio in BPH patients was even higher than in [the] general population," she wrote. "These BPH patients with risk alleles could be [a] potential population for targeted prostate cancer screening and follow-up."
Saaristo noted that the researchers have to validate their findings before the gene signature can be used clinically. "If clinical use is valid we have connections via [the] Institute of Biotechnology [at the] University of Tampere to help with the development towards commercial solutions," she said.
In the study, Saaristo and her colleagues analyzed biopsy samples from 262 patients diagnosed with histologically confirmed BPH who didn’t develop cancer and 254 patients originally diagnosed with BPH who did later develop prostate cancer. The group genotyped the patient samples for 100 SNP markers that they and other groups had previously linked to prostate cancer predisposition using a massARRAY platform from Sequenom.
Overall, 10 of the 100 SNPS showed a statistically significant association with future cancer development. One in particular, RS138213197 in the gene HOXB13, was more strongly predictive. According to the authors, BPH patients carrying the mutation had a 4.6 times higher risk of eventually developing cancer than those who did not carry the SNP.
Interest in developing predictive tests and risk-assessment tools for prostate cancer has been spurred by the desire to replace or augment prostate-specific antigen screening, which is known to suffer from a lack of specificity, resulting in substantial overdiagnosis.
Benign prostatic hyperplasia and prostate cancer are both usually discovered after men show elevated levels of PSA. According to the study authors, although BPH often explains the increase of PSA in absence of cancer, some, but not all, patients with BPA and elevated PSA go on to develop prostate cancer in follow-up after initial benign histology.
Several commercial tests have already entered the market that aim to shore up the specificity of PSA screening. Others — like Myriad's Prolaris and Genomic Health's Oncotype DX Prostate — offer additional prognostic information that can be used to rate a tumor's severity and aggressiveness for patients who already have a prostate cancer diagnosis (see related story, this issue).
According to the Finnish team, its approach ─ focusing on BPH and established prostate cancer risk markers ─ is unique. If the researchers are able to replicate their findings, one or more of the SNPs they identified could serve as a tool to pick out which BPH patients require closer monitoring or possibly preventive treatments.
The group is now planning to follow up with another study in a different population of patients, "potentially with the help of our foreign collaborators," Saaristo said.