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趋化因子受体CCR2基因分型在宫颈癌发生途径中的影响。

The influence of chemokine receptor CCR2 genotypes in the route to cervical carcinogenesis.

作者信息

Coelho Ana, Matos Ana, Catarino Raquel, Pinto Daniela, Sousa Hugo, Pereira Deolinda, Medeiros Rui

机构信息

Molecular Oncology/Virology, Instituto Português de Oncologia, Porto, Portugal.

出版信息

Gynecol Obstet Invest. 2007;64(4):208-12. doi: 10.1159/000106492. Epub 2007 Jul 30.

DOI:10.1159/000106492
PMID:17664883
Abstract

Invasive squamous cell carcinomas of the cervix arise from earlier, reversible precursor lesions called low- and high-grade squamous intraepithelial lesions (LSIL and HSIL, respectively). The aim of our study was to analyse the influence of the CCR2-64I polymorphism in the development of SIL due to its preponderant role in the cervical carcinogenesis and in the progression of these lesions to invasive cervical carcinoma. We conducted a case-control study, analyzing 565 Caucasian women from the north of Portugal. The CCR2-64I polymorphism was analysed through polymerase chain reaction followed by restriction fragment length polymorphism. The frequency of GG, GA and AA genotypes was 76.5, 23.5 and 0.0% respectively, in HSIL patients, and 87.8, 11.1 and 1.1% respectively, in the control group. The G allele frequency was 88.2% in the HSIL group and 93.4% in the control group. Regarding the A allele frequency, it was 11.8% in the HSIL group and 6.6% in the control group. Overall, the frequency of A carrier genotypes was higher in HSIL patients than in the control group (p = 0.013; OR = 2.21; 95%CI: 1.17-4.15), suggesting that CCR2-64I polymorphism might contribute to the establishment of HSIL, through the disruption of the naturally fragile immune response directed towards human papillomavirus infection.

摘要

宫颈浸润性鳞状细胞癌起源于更早的、可逆转的前驱病变,即低级别和高级别鳞状上皮内病变(分别为LSIL和HSIL)。由于CCR2 - 64I多态性在宫颈癌发生以及这些病变进展为浸润性宫颈癌过程中起主要作用,我们研究的目的是分析其在SIL发生发展中的影响。我们进行了一项病例对照研究,分析了来自葡萄牙北部的565名白人女性。通过聚合酶链反应及限制性片段长度多态性分析CCR2 - 64I多态性。在HSIL患者中,GG、GA和AA基因型的频率分别为76.5%、23.5%和0.0%,在对照组中分别为87.8%、11.1%和1.1%。HSIL组中G等位基因频率为88.2%,对照组中为93.4%。关于A等位基因频率,HSIL组为11.8%,对照组为6.6%。总体而言,HSIL患者中A携带者基因型的频率高于对照组(p = 0.013;OR = 2.21;95%CI:1.17 - 4.15),这表明CCR2 - 64I多态性可能通过破坏针对人乳头瘤病毒感染的天然脆弱免疫反应,促成HSIL的形成。

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Tumour necrosis factor alpha 308 G/A is a risk marker for the progression from high-grade lesions to invasive cervical cancer.肿瘤坏死因子α 308 G/A是高级别病变进展为浸润性宫颈癌的一个风险标志物。
Tumour Biol. 2014 Mar;35(3):2561-4. doi: 10.1007/s13277-013-1337-3. Epub 2013 Nov 7.
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IL-1RN VNTR polymorphism and genetic susceptibility to cervical cancer in Portugal.白细胞介素 1 受体拮抗剂 VNTR 多态性与葡萄牙宫颈癌遗传易感性。
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A comprehensive review on host genetic susceptibility to human papillomavirus infection and progression to cervical cancer.关于宿主对人乳头瘤病毒感染及进展为宫颈癌的遗传易感性的综合综述。
Indian J Hum Genet. 2011 Sep;17(3):132-44. doi: 10.4103/0971-6866.92087.
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Polymorphisms in chemokine and receptor genes and gastric cancer risk and survival in a high risk Polish population.趋化因子和受体基因多态性与波兰高危人群的胃癌风险及生存情况
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