Matrix metalloproteinase 1 gene polymorphism as a prognostic predictor of invasive cervical cancer
Matrix metalloproteinase 1 gene polymorphism as a prognostic predictor of invasive cervical cancer
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DOI：
10.1016/j.ygyno.2004.09.065
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发表时间：
2005-02-01
影响因子：
4.7
通讯作者：
Chu, TY
中科院分区：
文献类型：
--
作者：
Lai, HC;Chu, CM;Chu, TY
目标.虽然人乳头瘤病毒（HPV）感染是宫颈癌发生的主要决定因素，宿主遗传因素可能会赋予个体易感性和预后。基质金属蛋白酶1（MMP-1）是肿瘤发生的重要调节因子。在MMP-1基因启动子的核苷酸-1607处的鸟嘌呤插入（2G）多态性产生Ets-1结合位点，其增加转录活性。本研究旨在探讨MMP-1基因多态性与宫颈癌的关系及其预后意义。在这项研究中，通过毛细管电泳评估了135例高级鳞状上皮内病变（HSIL）和197例浸润性鳞状细胞癌（SCC）以及年龄匹配的对照组中的MMP-1多态性。检测MMP-1基因型与临床病理因素、HPV感染状况的关系。HSIL和SCC中2G等位基因的频率分别为64%和65%，与对照值（分别为66%和64%）无显著差异。2G等位基因与疾病的晚期相关（P = 0.03），而G等位基因在区域淋巴结转移患者中更常见（P = 0.02）。G/2G杂合子基因型患者的生存时间（中位数，55.3个月）显著长于G/G（50.3个月）或2G/2G基因型（43.9个月）（P = 0.02）。HPV感染状态与MMP-1基因型无明显相关性。MMP-1基因多态性与HSIL和SCC的发病风险无关，但与SCC的侵袭性和预后有关。MMP-1的杂合基因型可作为浸润性宫颈癌患者的预后指标。(C)2004年爱思唯尔公司All rights reserved.
Objectives. Whereas human papillomavirus (HPV) infection is the major determinant of cervical carcinogenesis, host genetic factors may confer individual susceptibility and prognosis. Matrix metalloproteinase 1 (MMP-1) is an important modulator of carcinogenesis. A guanine insertion (2G) polymorphism at nucleotide -1607 of the MMP-1 gene promoter creates an Ets-1-binding site, which increases transcription activity. The present study investigates the association between MMP-1 polymorphism and cervical neoplasia, and their prognostic significance.Methods. In this study, the MMP-1 polymorphism was assessed in 135 high-grade squamous intraepithelial lesions (HSILs) and 197 invasive squamous cell carcinomas (SCCs), and in age-matched controls, by capillary electrophoresis. The association of clinicopathological factors and HPV status with MMP-1 genotypes was tested.Result. Frequencies of the 2G allele in HSIL and SCC were 64% and 65%, respectively, which did not differ significantly from control values (66% and 64%, respectively). The 2G allele was associated with advanced stages of disease (P = 0.03), whereas the G allele was more common in patients with regional lymph node metastases (P = 0.02). The survival time in patients with the heterozygous genotype G/2G (median, 55.3 months) was significantly longer than those with either the G/G (50.3 months) or 2G/2G genotype (43.9 months) (P = 0.02). No significant correlation between HPV status and MMP-1 genotype was identified.Conclusions. The genetic polymorphisms of MMP-1 are not associated with the risk of HSIL and SCC, but with the invasiveness and prognosis of SCC. The heterozygous genotype of MMP-1 can be used as a prognostic marker in patients with invasive cervical cancer. (C) 2004 Elsevier Inc. All rights reserved.