Objectives
To investigate whether selected high-risk MMP7 single nucleotide polymorphisms influence tumor biology or clinical outcomes in patients with clinical early-stage prostate cancer undergoing prostatectomy.
Methods
Two hundred twelve human prostate cancer patients treated with radical prostatectomy were included in the study. Median follow-up was approximately 9.8 years. Genotyping was performed using TaqMan™ technology and custom-designed probes. Three single nucleotide polymorphisms within various regions of the MMP7 gene were assessed with correlation to age at diagnosis, margin status, extracapsular extension, lymph node metastasis, local recurrence and tumor survival in paraffin-embedded prostate tissue specimens from patients with early-stage prostate cancer receiving radical prostatectomy alone.
Results
Rs10895304 was the sole significant polymorphism. The SNP correlated to increased recurrence rates in post-prostatectomy patients (P<0.0094, Log Rank Test). The frequency of the homozygous dominant (A/A) is 74%, the heterozygote (A/G) is 20% and the homozygous recessive (G/G) is 6%. Multivariate analysis (using Chi square analysis) did not detect a confounding relationship between recurrence and age at diagnosis, PSA or Gleason score. None of the other assayed polymorphisms were significant, and no correlations were made to other clinical variables.
Conclusions
The G allele of the rs10895304 polymorphism is predictive of increased local recurrence risk in patients with clinically localized prostate cancer. 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 early post-operative radiation therapy to improve local control.
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