title: Genome-wide detection of allelic genetic variation to predict advanced-stage prostate cancer after radical prostatectomy using an exome SNP chip.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Urology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: Jong Jin
authors.initials: JJ
authors.lastname: Oh
authors.affiliation: Department of Electrical and Computer Engineering, Seoul National University, Seoul, Republic of Korea; School of Electrical Engineering, Korea University, Seoul, Republic of Korea.
authors.forename: Seunghyun
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Urology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: Sang Eun
authors.initials: SE
authors.lastname: Lee
authors.affiliation: Department of Urology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: Sung Kyu
authors.initials: SK
authors.lastname: Hong
authors.affiliation: Department of Urology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: Sangchul
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Urology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: Jung Ki
authors.initials: JK
authors.lastname: Jo
authors.affiliation: Department of Urology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: Jung Keun
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Department of Urology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea; Biomedical Research Institute, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: Jin-Nyoung
authors.initials: JN
authors.lastname: Ho
authors.affiliation: Department of Electrical and Computer Engineering, Seoul National University, Seoul, Republic of Korea.
authors.forename: Sungroh
authors.initials: S
authors.lastname: Yoon
authors.affiliation: Department of Urology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea. Electronic address: ssbyun@snubh.org.
authors.forename: Seok-Soo
authors.initials: SS
authors.lastname: Byun
mesh_terms: D000368:Aged; D000483:Alleles; D014408:Biomarkers, Tumor / Q000235:genetics*; D015331:Cohort Studies; D059472:Exome / Q000235:genetics; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D020641:Polymorphism, Single Nucleotide; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor
keywords: Exome array; Predictive value; Prostate cancer; Stage