title: Prostate cancer risk variants are not associated with disease progression.
abstract: BACKGROUND
  Currently used prognostic markers are limited in their ability to accurately predict disease progression among patients with localized prostate cancer. We examined 23 reported prostate cancer susceptibility variants for association with disease progression.
  
  
  METHODS
  Disease progression was explored among 4,673 Swedish patients treated for clinically localized prostate cancer between 1997 and 2002. Prostate cancer progression was defined according to primary treatment as a composed event reflecting termination of deferred treatment, biochemical recurrence, local progression, or presence of distant metastasis. Association between single variants, and all variants combined, were performed in Cox regression analysis assuming both log-additive and co-dominant genetic models.
  
  
  RESULTS
  Three of the 23 genetic variants explored were nominally associated with prostate cancer progression; rs9364554 (P = 0.041) on chromosome 6q25 and rs10896449 (P = 0.029) on chromosome 11q13 among patients treated with curative intent; and rs4054823 (P = 0.008) on chromosome 17p12 among patients on surveillance. However, none of these associations remained statistically significant after correction for multiple testing. The combined effect of all susceptibility variants was not associated with prostate cancer progression neither among patients receiving treatment with curative intent (P = 0.14) nor among patients on surveillance (P = 0.92).
  
  
  CONCLUSIONS
  We observed no evidence for an association between any of 23 established prostate cancer genetic risk variants and disease progression. Accumulating evidence suggests separate genetic components for initiation and progression of prostate cancer. Future studies systematically searching for genetic risk variants associated with prostate cancer progression and prognosis are warranted.
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Robert
authors.initials: R
authors.lastname: Szulkin
authors.forename: Erik
authors.initials: E
authors.lastname: Holmberg
authors.forename: Pär
authors.initials: P
authors.lastname: Stattin
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.forename: Sigun
authors.initials: S
authors.lastname: Zheng
authors.forename: Juni
authors.initials: J
authors.lastname: Palmgren
authors.forename: Henrik
authors.initials: H
authors.lastname: Grönberg
authors.forename: Fredrik
authors.initials: F
authors.lastname: Wiklund
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011467:Prostate / Q000473:pathology* / Q000601:surgery; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery