MDM2基因SNP309多态性与宫颈癌的相关性研究

目的：研究汉族妇女中MDM2基因SNP309多态性与宫颈癌易感性及临床病理学参数之间的关系。方法：用DNA抽提试剂盒从研究对象的外周血标本中抽提基因组DNA， 其中宫颈癌患者105例， 正常对照组140例； 用聚合酶链式反应-限制性片段长度多态 （PCR-RFLP） 和直接测序方法测定MDM2-SNP309单核苷酸多态基因型。结果：宫颈癌患者的MDM-SNP309 G等位基因频率显著高于对照组 （60.0% vs 48.6%， P=0.012； OR=1.59， 95% CI=1.11～2.28）； 宫颈癌与对照组之间的GG、 TG和TT等位基因型的分布差异有统计学意义， 其中GG等位基因型在宫颈细胞癌中的频率显著高于对照组 （36.2% vs 18.6%， P=0.016； OR=2.58，95% CI=1.19～5.61）。在宫颈癌组中， 淋巴转移阳性组MDM2-SNP309 GG等位基因型显著高于淋巴转移阴性组 （31.8% vs 11.5%， P<0.05）， SNP309单核苷酸多态性分布与肿瘤组织学类型、病理分级及肿瘤大小无关。结论:MDM2基因SNP309 GG基因型是宫颈癌发生的遗传易感因素， 与宫颈癌的淋巴转移发生有相关性。

Correlation between MDM2 Gene SNP309 Polymorphisms and Cervical Cancer

Correlation between MDM2 Gene SNP309 Polymorphisms and Cervical Cancer Pei JIANG1 , Jianxin LIU2 , Wen LI 1 , Xiaoxi ZENG1 , Jianxin TANG1 Correspondence to: Jianxin TANG, E-mail: jy1046@yahoo.com.cn 1 Green Packaging and Biological Nanotechnology Laboratory, Hu'nan Polytechnic University, Zhuzhou 412008, China 2 School of Info-physics and Geomatics Engineering, Central South University, Changsha 410083, China This work was supported by National Natural Science Foundation of China (No. 60871007) and Research Fund of Hu'nan Provincial Bureau of Education (No. 09C313) Abstract Objective: Mouse double minute 2 (MDM2) is a key negative feedback regulator of p53 activity. Recently it is shown that there is a correlation between a polymorphism in the SNP309 location, an intronic promoter, and the suscepti- bility to different cancers. In the Chinese population, however, there is still no report on the correlation between the SNP309 polymorphism and cervical cancer. To better understand the role of this polymorphism in the etiology of cervical cancer, we investigated the correlation between MDM2-SNP309 and risk of cervical cancer in Han women of Southern China. Meth? ods: Peripheral blood samples were obtained from patients with cervical cancer ( n = 105 ) and healthy controls ( n = 140 ). A DNA extracting kit was used for genomic DNA preparation. Genotyping was confirmed with polymerase chain reaction-re- striction fragment length polymorphism ( PCR-RFLP ) and direct DNA sequencing. Logistic regression analysis was used to calculate adjusted odds ratio ( OR ) and 95% confidence interval ( 95% CI ). Results: The SNP309 G allele frequency was significantly higher in the cervical cancer patients than in the controls ( 60.0%vs 48.6%, P = 0.012; OR = 1.59, 95% CI = 1.11-2.28 ). There were significant differences in distribution of the GG, TG, and TT allelotypes between the cervical cancer patients and the control group ( P < 0. 05 ). The GG genotype was more frequently found in the cervical cancer patients than in the controls (36.2% vs. 18.6%, P = 0.016; OR = 2.58, 95% CI = 1.19-5.61 ). Furthermore, we also found that the MDM2-SNP309 GG genotype was significantly associated with lymph node metastasis, but not with tumor histological type, tumor grade or size. Conclusions: Our findings show a significant association between a functional polymorphism in MDM2 and increased risk of developing cervical cancer in Chinese Han women. In addition, the SNP309 GG genotype may be a risk factor for lymph node metastasis of cervical cancer. Keywords MDM2; Gene; Polymorphism; Cervical cancer