title: Assessing the clinical role of genetic markers of early-onset prostate cancer among high-risk men enrolled in prostate cancer early detection.
abstract: BACKGROUND
  Men with familial prostate cancer and African American men are at risk for developing prostate cancer at younger ages. Genetic markers predicting early-onset prostate cancer may provide clinically useful information to guide screening strategies for high-risk men. We evaluated clinical information from six polymorphisms associated with early-onset prostate cancer in a longitudinal cohort of high-risk men enrolled in prostate cancer early detection with significant African American participation.
  
  
  METHODS
  Eligibility criteria include ages 35 to 69 with a family history of prostate cancer or African American race. Participants undergo screening and biopsy per study criteria. Six markers associated with early-onset prostate cancer [rs2171492 (7q32), rs6983561 (8q24), rs10993994 (10q11), rs4430796 (17q12), rs1799950 (17q21), and rs266849 (19q13)] were genotyped. Cox models were used to evaluate time to prostate cancer diagnosis and prostate-specific antigen (PSA) prediction for prostate cancer by genotype. Harrell's concordance index was used to evaluate predictive accuracy for prostate cancer by PSA and genetic markers.
  
  
  RESULTS
  Four hundred and sixty participants with complete data and ≥ 1 follow-up visit were included. Fifty-six percent were African American. Among African American men, rs6983561 genotype was significantly associated with earlier time to prostate cancer diagnosis (P = 0.005) and influenced prediction for prostate cancer by the PSA (P < 0.001). When combined with PSA, rs6983561 improved predictive accuracy for prostate cancer compared with PSA alone among African American men (PSA = 0.57 vs. PSA + rs6983561 = 0.75, P = 0.03).
  
  
  CONCLUSIONS
  Early-onset marker rs6983561 adds potentially useful clinical information for African American men undergoing prostate cancer risk assessment. Further study is warranted to validate these findings.
  
  
  CONCLUSIONS
  Genetic markers of early-onset prostate cancer have potential to refine and personalize prostate cancer early detection for high-risk men.
authors.affiliation: Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
authors.forename: Lucinda
authors.initials: L
authors.lastname: Hughes
authors.forename: Fang
authors.initials: F
authors.lastname: Zhu
authors.forename: Eric
authors.initials: E
authors.lastname: Ross
authors.forename: Laura
authors.initials: L
authors.lastname: Gross
authors.forename: Robert G
authors.initials: RG
authors.lastname: Uzzo
authors.forename: David Y T
authors.initials: DY
authors.lastname: Chen
authors.forename: Rosalia
authors.initials: R
authors.lastname: Viterbo
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Rebbeck
authors.forename: Veda N
authors.initials: VN
authors.lastname: Giri
mesh_terms: D000328:Adult; D001741:Black or African American; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D001706:Biopsy; D015331:Cohort Studies; D055088:Early Detection of Cancer / Q000379:methods; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017430:Prostate-Specific Antigen / Q000235:genetics; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; D005819:Genetic Markers; D017430:Prostate-Specific Antigen