The matrix metalloproteinase-7 polymorphism rs10895304 is associated with increased recurrence risk in patients with clinically localized prostate cancer.
The matrix metalloproteinase-7 polymorphism rs10895304 is associated with increased recurrence risk in patients with clinically localized prostate cancer.
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基质金属蛋白酶 7 多态性 rs10895304 与临床局限性前列腺癌患者复发风险增加相关。
DOI：
10.1016/j.ijrobp.2010.01.013
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Lu,Bo
中科院分区：
文献类型：
--
作者：
Jaboin,JerryJ;Hwang,Misun;Lopater,Zachary;Chen,Heidi;Ray,GeoffreyL;Perez,Carmen;Cai,Qiuyin;Wills,MarciaL;Lu,Bo
目的探讨选择性高危MMP7单核苷酸多态性是否影响临床早期前列腺癌行前列腺切除术患者的肿瘤生物学或临床预后。方法选取2012例行根治性前列腺切除术的前列腺癌患者作为研究对象。中位随访时间约为9.8年。采用TaqMan™技术和定制探针进行基因分型。在单独接受根治性前列腺切除术的早期前列腺癌患者石蜡包埋前列腺组织标本中，评估MMP7基因不同区域的三个单核苷酸多态性与诊断年龄、边缘状态、囊外延伸、淋巴结转移、局部复发和肿瘤生存的相关性。结果Rs10895304是唯一具有显著多态性的基因。SNP与前列腺切除术后患者复发率增加相关（P<0.0094， Log Rank检验）。纯合显性（A/A）为74%，杂合子（A/G）为20%，纯合隐性（G/G）为6%。多变量分析（使用卡方分析）未发现复发与诊断年龄、PSA或Gleason评分之间的混杂关系。其他分析的多态性均不显著，与其他临床变量无相关性。结论rs10895304基因G等位基因多态性可预测临床上局限性前列腺癌患者局部复发风险增加。对于这部分患者，单独的前列腺切除术可能不足以局部控制。这是一个新的和相关的标志物，应该评估改善患者的风险分层，这些患者可能是早期术后放射治疗的候选人，以改善局部控制。
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.