title: Common variants in IGF1 pathway genes and clinical outcomes after radical prostatectomy.
abstract: BACKGROUND
  Insulin-like growth factor-1 (IGF1) pathway plays a critical role in malignant transformation, and epidemiology studies have also shown that single nucleotide polymorphisms (SNPs) in IGF1 pathway genes are associated with prostate cancer risk. However, the clinical significance of these SNPs on prostate cancer aggressiveness and prognosis after radical prostatectomy (RP) has not been determined.
  
  
  METHODS
  We evaluated the associations of 4 common SNPs in IGF1 and IGF1R with age at diagnosis, preoperative prostate-specific antigen (PSA) level, pathologic Gleason score, pathologic stage, surgical margin, lymph node metastasis, and PSA recurrence in a cohort of 320 localized prostate cancer patients receiving RP. The prognostic significance on time to PSA recurrence was also assessed by Cox proportional hazards model.
  
  
  RESULTS
  IGF1 rs2946834 alleles/genotypes and an IGF1 specific haplotype AT, containing the minor allele of rs2946834, were associated (P ≤ 0.028) with a 1.49- to 2.22-fold higher risk of having advanced-stage prostate cancer. In addition, a genetic interaction profile consisting of IGF1 rs2946834 and IGF1R rs2016347 was significantly associated with PSA recurrence (P = 0.033).
  
  
  CONCLUSIONS
  Our study is the first to evaluate the impact of SNPs in IGF1 pathway genes on PSA recurrence. A genetic interaction between IGF1 rs2946834 and IGF1R rs2016347 might be a predictor of outcomes following RP.
authors: Department of Anatomy, School of Medicine, China Medical University, Taichung, Taiwan.
authors: Chi-Fen
authors: CF
authors: Chang
authors: Jiunn-Bey
authors: JB
authors: Pao
authors: Chia-Cheng
authors: CC
authors: Yu
authors: Chao-Yuan
authors: CY
authors: Huang
authors: Shu-Pin
authors: SP
authors: Huang
authors: Ying-Pi
authors: YP
authors: Yang
authors: Chun-Nung
authors: CN
authors: Huang
authors: Ta-Yuan
authors: TY
authors: Chang
authors: Bang-Jau
authors: BJ
authors: You
authors: Hong-Zin
authors: HZ
authors: Lee
authors: Tzyh-Chyuan
authors: TC
authors: Hour
authors: Bo-Ying
authors: BY
authors: Bao
mesh_terms: D000367:Age Factors; D000368:Aged; D006239:Haplotypes; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D018365:Neoplasm, Residual; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D017526:Receptor, IGF Type 1 / Q000235:genetics*
chemical_list: C583557:IGF1 protein, human; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D017430:Prostate-Specific Antigen