title: The matrix metalloproteinase-7 polymorphism rs10895304 is associated with increased recurrence risk in patients with clinically localized prostate cancer.
abstract: OBJECTIVE
  To evaluate whether selected high-risk matrix metalloproteinase-7 single nucleotide polymorphisms influence clinicopathologic outcomes in patients with early-stage prostate cancer.
  
  
  METHODS
  Two hundred twelve prostate cancer patients treated with radical prostatectomy were evaluated with a median follow-up of 9.8 years. Genotyping was performed using hybridization with custom-designed allele-specific probes. Three single nucleotide polymorphisms within the matrix metalloproteinase-7 gene were assessed with respect to age at diagnosis, margin status, extracapsular extension, lymph node involvement, recurrence-free survival, and overall survival in paraffin-embedded prostate tissue specimens from patients with early-stage prostate cancer who underwent radical prostatectomy.
  
  
  RESULTS
  Rs10895304 was the sole significant polymorphism. The A/G genotype of rs10895304 had a statistically significant association with recurrence-free survival in postprostatectomy patients (p = 0.0061, log-rank test). The frequency of the risk-reducing genotype (A/A) was 74%, whereas that of the risk-enhancing genotypes (A/G and G/G) were 20% and 6%, respectively. Multivariable Cox regression analyses detected a significant association between rs10895304 and recurrences after adjustment for known prognostic factors. The G allele of this polymorphism was associated with increased risk of prostate cancer recurrence (adjusted hazards ratio, 3.375; 95% confidence interval 1.567-7.269; p < 0.001). The other assayed polymorphisms were not significant, and no correlations were made to other clinical variables.
  
  
  CONCLUSIONS
  The A/G genotype of rs10895304 is predictive of decreased recurrence-free survival in patients with clinically localized prostate cancer. Our data suggest that for this subset of patients, prostatectomy alone may not be adequate for local control. This is a novel and relevant marker that should be evaluated for improved risk stratification of patients who may be candidates for adjuvant radiation therapy to improve local control.
authors.affiliation: Department of Radiation Oncology, Vanderbilt University, Nashville, TN, USA.
authors.forename: Jerry J
authors.initials: JJ
authors.lastname: Jaboin
authors.forename: Misun
authors.initials: M
authors.lastname: Hwang
authors.forename: Zachary
authors.initials: Z
authors.lastname: Lopater
authors.forename: Heidi
authors.initials: H
authors.lastname: Chen
authors.forename: Geoffrey L
authors.initials: GL
authors.lastname: Ray
authors.forename: Carmen
authors.initials: C
authors.lastname: Perez
authors.forename: Qiuyin
authors.initials: Q
authors.lastname: Cai
authors.forename: Marcia L
authors.initials: ML
authors.lastname: Wills
authors.forename: Bo
authors.initials: B
authors.lastname: Lu
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000368:Aged; D000704:Analysis of Variance; D006801:Humans; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000235:genetics*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000401:mortality; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology
chemical_list: D020783:Matrix Metalloproteinase 7