Arechavaleta-Velasco Fabian, Cuevas-Antonio Rocio, Dominguez-Lopez Pablo, Estrada-Moscoso Isaias, Imani-Razavi Fazlollah Shahram, Zeferino-Toquero Moises, Diaz-Cueto Laura
Research Unit in Reproductive Medicine, UMAE Hospital de Gineco-Obstetricia No. 4 Luis Castelazo Ayala, IMSS, Rio Magdalena 289, Sexto Piso, Tizapan San Angel, CP 01090, México, D. F., Mexico.
Med Oncol. 2014 Aug;31(8):132. doi: 10.1007/s12032-014-0132-3. Epub 2014 Jul 18.
Increased levels of matrix metalloproteinase-8 (MMP-8) have been associated with tumor grade and stage in ovarian cancer. Also, it has been reported that higher concentrations of this enzyme in fluid from malignant ovarian cysts compared with benign ovarian cysts. However, no genetic analysis has been conducted yet to assess the contribution of MMP-8 polymorphisms in ovarian cancer. Thus, this study was performed to investigate the frequencies of MMP-8 genotypes in Mexican women with ovarian cancer. MMP-8 promoter genotypes were examined in 35 malignant ovarian tumors, 51 benign tumors, and 37 normal ovary tissues. Two single nucleotide polymorphisms were selected and characterized using polymerase chain reaction-restriction fragment length polymorphism analysis. The chi-square test was used to calculate statistical significance. Haplotype analysis was performed using the SNPstats web tool. Of the two polymorphisms, only the MMP-8 -799 T/T genotype was significantly associated with an increased risk of ovarian cancer (OR 3.78, 95 % CI 1.18-12.13). The Kaplan-Meier analysis for this polymorphism showed that patients with the T/T genetic variant had a tendency toward significant worse overall survival compared with patients with the C/C + C/T genotypes. Haplotype analysis revealed no significant differences in haplotype distribution between benign ovarian tumors, malignant ovarian cancer, and controls. This study suggests that MMP-8 promoter gene polymorphism -799 T/T is significantly associated with an increased risk of ovarian cancer in Mexican women.
基质金属蛋白酶-8（MMP-8）水平升高与卵巢癌的肿瘤分级和分期相关。此外，据报道，恶性卵巢囊肿液体中该酶的浓度高于良性卵巢囊肿。然而，尚未进行基因分析来评估MMP-8多态性在卵巢癌中的作用。因此，本研究旨在调查墨西哥卵巢癌女性中MMP-8基因型的频率。对35例恶性卵巢肿瘤、51例良性肿瘤和37例正常卵巢组织进行了MMP-8启动子基因型检测。使用聚合酶链反应-限制性片段长度多态性分析选择并鉴定了两个单核苷酸多态性。采用卡方检验计算统计学意义。使用SNPstats网络工具进行单倍型分析。在这两个多态性中，只有MMP-8 -799 T/T基因型与卵巢癌风险增加显著相关（OR 3.78，95%CI 1.18-12.13）。对该多态性的Kaplan-Meier分析表明，与C/C + C/T基因型患者相比，T/T基因变异患者的总生存期有显著较差的趋势。单倍型分析显示，良性卵巢肿瘤、恶性卵巢癌和对照组之间的单倍型分布无显著差异。本研究表明，MMP-8启动子基因多态性-799 T/T与墨西哥女性卵巢癌风险增加显著相关。
