Genome-wide detection of allelic genetic variation to predict advanced-stage prostate cancer after radical prostatectomy using an exome SNP chip.

Abstract

Objectives: Genetic variations among patients with prostate cancer (PCa) who underwent radical prostatectomies were evaluated to predict advanced stage above T3 using an exome single nucleotide polymorphism (SNP) chip array.

Materials and methods: We collected data of genetic SNP variants from 820 patients with PCa who underwent radical prostatectomy (RP) using a custom HumanExome BeadChip v1.0 (Illumina Inc.). We selected the SNPs that were most significantly associated with advanced-stage PCa (>= T3) among the 242,186 SNPs that were genotyped, and we compared the accuracies of the associations using a multivariate logistic model that incorporated clinical factors and clinicogenetic factors.

Results: Among the total cohort, 360 patients (43.9%) had advanced pathologic stage (>= T3) after RP, of whom 262 (32.0%) had extracapsular extensions, 79 (9.6%) had seminal vesicle invasions, and 10 (1.3%) had bladder neck invasions. The exome array analysis indicated that 5 SNPs (rs6804162, rs8055236, rs56335308, rs6104, and rs12618769) were significant for predicting T3 stage after RP in patients with PCa. These genetic markers were significant factors after adjusting for other clinical parameters, and they increased the accuracy of a multivariate model for predicting advanced stage of PCa (83.9%-87.2%, P = 0.0001).

Conclusions: Based on a genetic array, the selected SNPs were found to be independent predictors for advanced stage after RP, and the addition of individualized genetic information effectively enhanced the accuracy of predicting advanced-stage disease. These results should be validated in another independent cohort.