Prostate cancer risk genes also predict disease progression
MedWire News: Five out of 26 single nucleotide polymorphisms (SNPs) recently associated with a risk for prostate cancer are also able to predict progression in men who already have the disease, say researchers.
"By examining how inherited variation affects disease progression, we will further advance our understanding of prostate cancer prognosis, with the ultimate goal of better targeting aggressive treatment to patients most likely to suffer from disease recurrence, metastasis, and death," say John Witte, from the University of California in San Francisco, USA, and colleagues.
The group genotyped the 26 SNPs in a cohort of 788 men with aggressive prostate cancer treated with radical prostatectomy or radiotherapy, in order to establish whether any patients whose tumors had progressed following treatment were risk allele carriers.
After a median of 26.8 months, 228 patients experienced progression, defined as having a posttreatment prostate-specific antigen (PSA) level of more than 0.3 ng/ml after surgery, and having a 2 ng/ml increase in PSA above the posttreatment nadir after radiotherapy. Initiation of salvage therapy also indicated progression.
Five of the 26 SNPs (rs12621278, rs629242, rs9364554, rs4430796, and rs5945572) were independently associated with prostate cancer progression after multivariate analysis, adjusted for diagnostic PSA level, Gleason score, disease stage, and primary mode of treatment.
Witte and team found that for every additional risk allele carried (a total of seven among the five SNPs), patients had an estimated 29% increase in the risk for prostate cancer progression.
Furthermore, patients with four to seven risk alleles had a 2.19-fold increased risk for progression compared with patients who carried less than one risk allele.
The SNP most significantly independently associated with prostate cancer progression was located in the ITGA6 gene, rs12621278, which gave AG genotype carriers a 2.4-fold increased risk for progression compared with carriers of the AA genotype.
Witte et al also observed that the more risk alleles a patient carried, the shorter the time to disease progression, ranging from 54.3 months for carriers of less than one allele to 43.5 months for those with four to seven.
"By identifying new progression markers, key insights may be gained in understanding the biological mechanism of disease process," the researchers conclude in the journal Cancer Epidemiology Biomarkers and Prevention.
MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010
By Sarah Guy