Androgen receptor polymorphisms and risk of biochemical failure among prostatectomy patients

Prostate. 2004 Sep 1;60(4):343-51. doi: 10.1002/pros.20060.

Abstract

Background: Little is known about the role of inherited genotypes in prostate cancer (PC) progression. This prospective study evaluated the predictive value of androgen receptor (AR) polymorphisms (CAG and GGC repeats) among prostatectomy patients.

Methods: We studied 354 patients registered at M. D. Anderson Cancer Center from 1991 to 2001. Kaplan-Meier and Cox proportional hazard analyses were used.

Results: During an average follow-up of 56 months, 66 (19%) post-prostatectomy patients experienced biochemical failure (BF). Patients with higher CAG repeats (CAG > or = 24) had significantly longer BF-free survival (BFFS) than those with fewer repeats (CAG < or = 23) (P = 0.04). Higher CAG repeats were significantly associated with lower BF risk among Whites and African Americans. Among Whites, longer CAG repeats (relative risk (RR) = 0.45, P = 0.03) and Gleason score > or = 8 (RR = 19.33, P = 0.005) remained significant BFFS predictors in multivariate analysis. GGC repeats were not associated with BF.

Conclusions: Our data showed that an inherited polymorphism (CAG repeats) in the AR is related to differences in genetic susceptibility to BF, supporting the hypothesis that increased AR activity may play a role in PC progression.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery*
  • Aged
  • Disease Progression
  • Disease-Free Survival
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Predictive Value of Tests
  • Prospective Studies
  • Prostate-Specific Antigen / blood*
  • Prostatectomy*
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / surgery*
  • Receptors, Androgen / genetics*
  • Risk Factors
  • Treatment Outcome
  • Trinucleotide Repeats

Substances

  • Receptors, Androgen
  • Prostate-Specific Antigen