Yin C M, Yao Y F, Yan Z L, Yang H Y
Department of Gynecologic Oncology, the Third Affiliated Hospital of Kunming Medical University, Kunming 650118, China.
Zhonghua Fu Chan Ke Za Zhi. 2017 May 25;52(5):320-326. doi: 10.3760/cma.j.issn.0529-567X.2017.05.006.
To detect mutations of p53 gene 2-4 exons from peripheral blood and to explore their relevance in HPV16-positive cervical cancer susceptibility and clinical significance. Collected firstly cases from the Third Affiliated Hospital of Kunming Medical University from October 2012 to April 2014, included 167 cases HPV16-postive cervical cancer and 160 cases HPV-negative healthy women. Genomic DNA from the host peripheral venous blood was taken, mutations of p53 gene 2-4 exons were analyzed with software DNAstar after PCR and bidirectional sequencing. Meanwhile, mutations of p53 gene 2-4 exons among different clinicopathological characteristics in HPV16-postive cervical cancer were distinguished. (1) Three mutations and an 16-bp insertion/deletion sequences were found in p53 gene exons 2-4, included C/G mutation of single nucleotide polymorphism (SNP) 11827 in intron2, A/C mutation of SNP11992 in intron3, C/G mutation in codon 72 (rs1042522) of exon4 and 16-bp (acctggagggctgggg) repeat insertion or deletion in intron3 (rs17878362), while deletion recorded as A1, insertion recorded as A2. No significant differences were found in each point allele and genotype frequency (>0.05) . (2) Stratified analysis for cervical cancer group resulted with some differences. Compared group of non-squamous carcinoma with squamous carcinoma group, there were obviously decreased in allete A2 [11.8% (4/34) vs 3.5% (10/284) ; χ(2)=4.90, =0.027], genotype A1A2 [4/17 vs 7.0% (10/142) ; χ(2)=5.14, =0.023], and haplotype C-A2 [11.8% (4/34) vs 3.5% (10/284) ; χ(2)=4.91, =0.027]. Compared with poorly differentiated group, allele C of SNP11827 and rs1042522 were obviously decreased in medium high differentiation group [50.8% (61/120) vs 38.8% (62/160) ; χ(2)=4.07, =0.044], while haplotype G-A1 were apparently higher [49.2% (59/120) vs 61.2% (98/160) ; χ(2)=4.07, =0.044], genotype GG of SNP11827 and rs1042522 were obviously decreased in superficial myometrial invasion depth group than that in deep myometrial invasion depth group [46.3% (25/54) vs 21.1% (8/38) ; χ(2)=7.06, =0.029]. No significant differences were found between stage Ⅰ and Ⅱ, pelvic lymph node metastasis or not (all >0.05) . No obvious correlation is found between polymorphisms in exons 2-4 of p53 gene and susceptibility of HPV16-postive cervical cancer. But the patient with allete C and A2, genotype GG and A1A2, haplotype C-A2 and G-A1 may be increase risk of poorly differentiation, deep muscular invasion and bad pathological type. Analysis of p53 gene polymorphism may be provide a basis for the prognosis evaluation and individualized treatment of cervical cancer.
检测外周血中p53基因2 - 4外显子的突变情况，探讨其与HPV16阳性宫颈癌易感性的相关性及临床意义。首先收集2012年10月至2014年4月昆明医科大学第三附属医院的病例，包括167例HPV16阳性宫颈癌患者和160例HPV阴性健康女性。采集宿主外周静脉血的基因组DNA，经PCR及双向测序后，用DNAstar软件分析p53基因2 - 4外显子的突变情况。同时，区分HPV16阳性宫颈癌不同临床病理特征中p53基因2 - 4外显子的突变情况。（1）在p53基因外显子2 - 4中发现3个突变及1个16bp的插入/缺失序列，包括内含子2中单一核苷酸多态性（SNP）11827的C/G突变、内含子3中SNP11992的A/C突变、外显子4密码子72（rs1042522）的C/G突变以及内含子3中16bp（acctggagggctgggg）重复序列的插入或缺失（rs17878362），缺失记为A1，插入记为A2。各点等位基因和基因型频率差异均无统计学意义（>0.０5）。（2）宫颈癌组分层分析有一些差异。非鳞癌组与鳞癌组相比，等位基因A2明显降低[11.8%（4/34）对3.5%（10/284）；χ² = 4.90，P = 0.027]，基因型A1A2[4/17对7.0%（10/142）；χ² = 5.14，P = 0.023]，单倍型C - A2[11.8%（4/34）对3.5%（10/284）；χ² = 4.91，P = 0.027]。与低分化组相比，中高分化组SNP11827和rs1042522的等位基因C明显降低[50.8%（61/120）对3８.8%（62/160）；χ² = 4.07，P = 0.044]，而单倍型G - A1明显升高[49.2%（59/120）对61.2%（98/160）；χ² =４.07，P = 0.044]，浅肌层浸润深度组SNP11827和rs1042522的基因型GG明显低于深肌层浸润深度组[46.3%（25/54）对21.1%（8/38）；χ² = 7.06，P = 0.029]。Ⅰ期与Ⅱ期、有无盆腔淋巴结转移之间差异均无统计学意义（均>0.０5）。p53基因外显子2 - 4多态性与HPV16阳性宫颈癌易感性无明显相关性。但携带等位基因C和A2、基因型GG和A1A2、单倍型C - A2和G - A1的患者可能增加低分化、深肌层浸润及病理类型差的风险。p53基因多态性分析可为宫颈癌的预后评估及个体化治疗提供依据。
