Does genotyping of risk‐associated single nucleotide polymorphisms improve patient selection for prostate biopsy when combined with a prostate cancer risk calculator?

Abstract

The predictive performance of the clinical model was only slightly improved by adding MGRS questioning the real clinical added value with regards to the cost of genetic testing and performance of current inexpensive clinical risk-calculators.

Multiplex pyrosequencing assay using AdvISER-MH-PYRO algorithm: a case for rapid and cost-effective genotyping analysis of prostate cancer risk-associated SNPs

“…As evidenced by this study, multiplexing has proved to be particularly relevant when developing new rapid, robust, reliable, cleaner and cost-effective SNP genotyping assays. While the added clinical value of MGRS based on 9 PCa risk-associated SNPs proved indeed not bring a major benefit as previously discussed [ 5 ], it was technologically interesting to repeat this SNP analysis using the multiplex pyrosequencing method, especially because this method is widely applicable to a range of other clinical and/or research applications, all relying also on MGRS computation, and therefore requiring multi-SNP genotyping for each patient. Such applications are currently developed in a wide range of diseases, including coronary heart disease [ 18 ], liver diseases [ 19 ] and acute lymphoblastic leukemia [ 20 ].…”

“…Kader et al computed MGRS based on 33 established PCa risk-associated SNPs and demonstrated the potential added value of the score for PCa risk prediction [ 4 ]. More recently, a MGRS computed from a set of nine published SNPs (rs1016343, rs16901979, rs6983267, rs4242382, rs10993994, rs10896449, rs4430796, rs1859962, and rs5945619) improved the performance of a clinical risk-calculator in predicting prostate biopsy result [ 5 ]. The predictive performance of the integrated clinico-genetic model (AUC = 0.781) was higher than the predictive performance of the clinical score alone (AUC = 0.770).…”

“…In the present study, two multiplex assays were developed consisting of a quadruplex and a quintuplex PCR, each followed by pyrosequencing analysis for genotyping a set of PCa-related SNPs (n=9) [ 5 ]. The dispensation order was selected using SENATOR and multiplex pyro-signals were analyzed with an adapted version of AdvISER-M-PYRO (named AdvISER-MH-PYRO), which integrates a new function allowing bi-allelic SNP genotyping.…”

Androgen Receptor Polymorphism-Dependent Variation in Prostate-Specific Antigen Concentrations of European Men

“…By creating a risk profile containing a combination of SNPs identified through GWAS studies associated with prostate cancerrisk or changes in PSA-levels, some groups have aimed at constructing genetic risk adjusted PSA cutoff levels (43,44). Others have combined the risk profiles with the measured PSA in the selection of men that should be referred to biopsy (45)(46)(47)(48)(49)(50). However, the results have been promising but not convincing.…”

“…However, the results have been promising but not convincing. Some did not find that the genetic profile enhanced the outcome at all (46), whereas others reported an improvement, but often not large enough to alone support genetic testing as a clinical strategy (45,47,48,50). These studies shared certain SNPs, while other SNPs were study specific.…”