title: Clinical implications of family history of prostate cancer and genetic risk single nucleotide polymorphism (SNP) profiles in an active surveillance cohort.
abstract: OBJECTIVE
  To explore the potential prognostic role of family history (FH) of prostate cancer and prostate cancer risk single nucleotide polymorphisms (SNPs) in patients undergoing active surveillance (AS) for prostate cancer. This is the first study to date, which has investigated the potential prognostic role of SNP profiles in an AS cohort
  
  
  METHODS
  FH data were collected from patients in the Royal Marsden Hospital AS study. In all, 39 prostate cancer-risk SNPs identified from published genome wide association studies (GWAS) were genotyped using the Sequenom Platform and TaqMan™ assays from available DNA. The cumulative genetic-risk scores for each patient were then calculated using the weighted effect estimated from previous GWAS (log-additive model). FH status and the genetic-risk scores were assessed against adverse outcomes in AS, time to treatment and adverse histology on repeat biopsy, using univariable and multivariable Cox regression models to address time to treatment; and binary logistic regression to address biopsy upgrade.
  
  
  RESULTS
  Of 471 patients, 55 (13.6%) had adverse histology on repeat biopsies and 145 (30.8%) had deferred treatment. On univariate analysis, there was no significant relationship between FH of prostate cancer in any degree of relation, and adverse histology or time to treatment. For risk score analyses, 386 patients' DNA was studied; and there was also no relationship found between the calculated genetic risk scores and adverse histology or time to treatment (P = 0.573 and P = 0.965, respectively). The retrospective study design and the few events were the main limitation of the study.
  
  
  CONCLUSIONS
  There is currently insufficient data to support the use of FH status or prostate cancer SNP profile risk scores as prognostic factors in AS and these should not be used to influence management decisions. As more genetic variants are discovered this may change and should be reassessed in multicentre AS cohorts.
authors: Oncogenetics team, The Institute of Cancer Research.
authors: Chee L
authors: CL
authors: Goh
authors: Edward J
authors: EJ
authors: Saunders
authors: Daniel A
authors: DA
authors: Leongamornlert
authors: Malgorzata
authors: M
authors: Tymrakiewicz
authors: Karen
authors: K
authors: Thomas
authors: Elizabeth D
authors: ED
authors: Selvadurai
authors: Ruth
authors: R
authors: Woode-Amissah
authors: Tokhir
authors: T
authors: Dadaev
authors: Nadiya
authors: N
authors: Mahmud
authors: Elena
authors: E
authors: Castro
authors: David
authors: D
authors: Olmos
authors: Michelle
authors: M
authors: Guy
authors: Koveela
authors: K
authors: Govindasami
authors: Lynne T
authors: LT
authors: O'Brien
authors: Amanda L
authors: AL
authors: Hall
authors: Rosemary A
authors: RA
authors: Wilkinson
authors: Emma J
authors: EJ
authors: Sawyer
authors: Ali Amin
authors: AA
authors: Al Olama
authors: Douglas F
authors: DF
authors: Easton
authors: Zsofia
authors: Z
authors: Kote-Jarai
authors: Chris C
authors: CC
authors: Parker
authors: Rosalind A
authors: RA
authors: Eeles
mesh_terms: D000368:Aged; D005190:Family; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D012189:Retrospective Studies; D018570:Risk Assessment; D018571:Sentinel Surveillance; D006113:United Kingdom / Q000453:epidemiology
keywords: active surveillance; family history; genetic risk profiles; prostate cancer