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白细胞介素-8和基质金属蛋白酶-7基因多态性与早期宫颈癌发生及淋巴结转移的相关性

Correlation of polymorphism of IL-8 and MMP-7 with occurrence and lymph node metastasis of early stage cervical cancer.

作者信息

Wu Suhui, Lu Shi, Tao Huijuan, Zhang Li, Lin Weifeng, Shang Haixia, Xie Jun

机构信息

Department of Postgraduate, the First Hospital, Shanxi Medical University, Taiyuan, 030001, China.

Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

出版信息

J Huazhong Univ Sci Technolog Med Sci. 2011 Feb;31(1):114-119. doi: 10.1007/s11596-011-0161-5. Epub 2011 Feb 19.

Abstract

The IL-8 and MMP-7 genes participate in the carcinogenesis of many malignancies, but the role of both genes in cervical cancer is not fully elucidated. The aim of this study was to determine the frequency of IL-8 and MMP-7 gene mutations and to assess their effects on the risk of early stage cervical cancer and lymph node metastasis. The clinical stage and histological grade of cervical cancer were also studied. The peripheral blood from the patients with early stage cervical cancers and normal controls was collected and the DNA was extracted. The incidence of IL-8 and MMP-7 gene mutations was assessed by using tetra-primer amplification refractory mutation system polymerase chain reaction (ARMS PCR) and restriction fragment length polymorphism (RFLP). The data were statistically analyzed by x2 test. The results showed that: (1) The genotype frequency of IL-8 -251AT and TT was significantly higher in the cervical cancer group than in the normal control group (OR=2.290 and 2.619 respectively, P=0.001), and it was also higher in the lymphatic metastasis group than that without metastasis (OR=2.917, P=0.035); (2) The frequency of MMP-7 -181G/G genotype was significantly higher in the cervical cancer group and in the lymphatic metastasis group (P<0.05); (3) The incidence of IL-8 mutation was two times higher in IIa cervical cancer group than in Ib1 and Ib2 cervical cancer group (P=0.006). For the MMP-7 gene, there was statistically significant difference in the incidence of mutation between the Ib1, Ib2 and the IIa (P=0.000); (4) Different histological types and different grades of cervical cancer had different incidence of mutations, statistically. It was suggested that there was significant difference in the genotype of IL-8 -251TT and MMP-7 -181GG polymorphism between the cervical cancer group and the lymph node metastasis group. Moreover, individuals with IL-8 T allele or MMP-7 G allele carriers were at significantly higher risk of cervical cancer, particularly the early (IIa) and medium, poorly differentiated cervical cancer (G2+G3).

摘要

白细胞介素-8(IL-8)和基质金属蛋白酶-7(MMP-7)基因参与多种恶性肿瘤的发生发展,但这两个基因在宫颈癌中的作用尚未完全阐明。本研究旨在确定IL-8和MMP-7基因突变的频率,并评估其对早期宫颈癌风险及淋巴结转移的影响。同时还研究了宫颈癌的临床分期和组织学分级。收集早期宫颈癌患者及正常对照者的外周血并提取DNA。采用四引物扩增阻滞突变系统聚合酶链反应(ARMS PCR)和限制性片段长度多态性(RFLP)评估IL-8和MMP-7基因突变的发生率。数据采用x²检验进行统计学分析。结果显示:(1)宫颈癌组中IL-8 -251A>T和TT基因型频率显著高于正常对照组(OR分别为2.290和2.619,P = 0.001),且在有淋巴结转移组中也高于无转移组(OR = 2.917,P = 0.035);(2)MMP-7 -181G/G基因型频率在宫颈癌组和有淋巴结转移组中显著更高(P < 0.05);(3)IIa期宫颈癌组中IL-8基因突变发生率是Ib1和Ib2期宫颈癌组的两倍(P = 0.006)。对于MMP-7基因,Ib1、Ib2期与IIa期之间突变发生率存在统计学显著差异(P = 0.000);(4)不同组织学类型和不同分级的宫颈癌突变发生率存在统计学差异。提示宫颈癌组与淋巴结转移组之间IL-8 -251TT和MMP-7 -181GG多态性基因型存在显著差异。此外,携带IL-8 T等位基因或MMP-7 G等位基因的个体患宫颈癌的风险显著更高,尤其是早期(IIa期)以及中、低分化宫颈癌(G2 + G3)。

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