TP53基因第72密码子及内含子3 16碱基插入/缺失多态性与宫颈癌风险的关联

Association of TP53 codon 72 and intron 3 16-bp Ins/Del polymorphisms with cervical cancer risk.

作者信息

Laprano Tatiana Dantas Rodrigues, Lemos Erika Hardy, Cunha Lia Moreira Pinto, Júnior José Eleutério, de SousaTeles Rosiane Alves, Rabenhorst Silvia Helena Barem

机构信息

Department of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.

出版信息

Tumour Biol. 2014 Aug;35(8):7435-40. doi: 10.1007/s13277-014-1988-8. Epub 2014 Apr 30.

Abstract

Cervical cancer incidence has grown worldwide, with it being a more significant problem in developing countries. Invasive squamous cell cervical cancers are preceded by a long phase of preinvasive disease, known as cervical intraepithelial neoplasia. Cervical cancer can develop when the virus takes advantage of any TP53 gene dysfunction of the host organism. TP53 is responsible for encoding the tumor suppressor p53 phosphoprotein, which helps preserve genome integrity. Currently, many studies have focused on genetic polymorphisms as an important contribution to cancer susceptibility, but few related to cervical intraepithelial neoplasia (CIN). Thus, the present study aimed to see whether patients with suspected CIN had TP53 gene polymorphisms that might have contributed to the development of neoplasia. This study included 133 women who were referred to the Cervical Pathology Clinic of the Maternity School Assis Chateaubriand MEAC for suspected cervical lesions. Polymorphism genotyping was carried out by the PCR-RFLP technique using DNA extracted from patients' blood. The most frequent genotype in both CIN(+) and CIN(-) patients was Arg/Pro TP53 codon 72 and A1A1 for 16-bp Del in intron 3. No risk of cervical cancer was found for the polymorphisms studied. However, a significant association was found when the two polymorphisms were combined: patients with the A1A1/ArgPro genotype were statistically more frequent in the CIN(-) group (p = 0.042), while A2A2-A1A2/ProArg was significantly more frequent in the CIN(+) group. The results of our study suggest that combined analysis of TP53 polymorphisms Arg72Pro and 16-bp Ins/Del may help to monitor the development of CIN in Brazilian women.

摘要

宫颈癌发病率在全球范围内呈上升趋势,在发展中国家更是一个更为严重的问题。浸润性鳞状细胞宫颈癌之前存在一个漫长的癌前病变阶段,称为宫颈上皮内瘤变。当病毒利用宿主生物体的任何TP53基因功能障碍时,宫颈癌就可能发生。TP53负责编码肿瘤抑制蛋白p53,该蛋白有助于维持基因组完整性。目前,许多研究都聚焦于基因多态性对癌症易感性的重要影响,但与宫颈上皮内瘤变(CIN)相关的研究较少。因此,本研究旨在探讨疑似CIN患者是否存在可能导致瘤变发生的TP53基因多态性。本研究纳入了133名因疑似宫颈病变而转诊至阿西斯·夏多布里昂母婴学校MEAC宫颈病理诊所的女性。使用从患者血液中提取的DNA,通过PCR-RFLP技术进行多态性基因分型。CIN(+)和CIN(-)患者中最常见的基因型分别是TP53密码子72的Arg/Pro以及内含子3中16-bp缺失的A1A1。在所研究的多态性中未发现患宫颈癌的风险。然而,当将这两种多态性结合起来时发现了显著关联:A1A1/ArgPro基因型的患者在CIN(-)组中在统计学上更为常见(p = 0.042),而A2A2 - A1A2/ProArg在CIN(+)组中更为常见。我们的研究结果表明,对TP53多态性Arg72Pro和16-bp Ins/Del进行联合分析可能有助于监测巴西女性CIN的发展。

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