TLR9基因启动子区多态性与宫颈癌的相关性研究

发布时间：2018-02-16 14:06

本文关键词： Toll样受体9 宫颈癌发生发展单核苷酸多态性相关性　出处：《昆明医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：[目的]探讨TLR9基因启动子区单核苷酸多态性位点(SNPs) rs352139 CT、rs352140CT和rs5743836AG与宫颈癌发生发展的相关性。[方法]根据“知情同意”原则,选取云南地区汉族女性人群中宫颈癌患者253例,癌前病变患者92例,正常健康体检者330例,采用TaqMan探针基因分型的方法对上述SNP位点进行基因分型,并构建单倍型,评估上述3个SNP位点的等位基因、基因型以及单倍型与宫颈癌发生发展的相关性。[结果]1.TLR9 基因启动子区 SNP 位点 rs352139(CT)、rs352140(CT)、rs5743836(AG)的基因型和等位基因在各组间的分布频率差异均无统计学意义(P0.05)。2.连锁不平衡分析结果显示:在癌症组和对照组中,rs352139 (CT)与rs5743836 (AG),rs352140 (CT)与 rs5743836 (AG)间存在强连锁,D'值大于0.8。3.根据连锁不平衡结果构建的rs352139 (CT)、rs352140 (CT)和rs5743836(AG)的单倍型在癌症组和对照组中的分布频率差异无统计学意义(P0.05)。4.对宫颈癌组进行分层分析,研究结果显示TLR9基因rs352139、rs352140和rs5743836位点等位基因、基因型频率在鳞癌组与非鳞癌组、临床Ⅰ期与临床Ⅱ期之间比较无统计学差异,P值0.05。但是,TLR9基因启动子区rs352139等位基因T的频率在分化好组显著高于分化差组,两组比较差异有统计学意义(P=0.029, OR=0.629 95%CI=[0.414～0.957])。rs352139 位点等位基因 C 的频率在浅肌层组和深肌层组中分布具有显著差异性(P=0.038, χ2=4.299),其中等位基因C的频率在深肌层组明显高于浅肌层组(43.8%、32.7%)。TLR9基因启动子区rs352139位点在有淋巴结转移和无淋巴结转移的比较中,等位基因频率和基因型频率在两组比较中差异有统计学意义(P=0.006和P=0.025),其中C/C基因型频率在无淋巴结转移组明显高于有淋巴结转移组(20.3% vs 4.7%)。[结论]1.在云南汉族女性群体中,TLR9基因启动子区的3个SNP位点rs352139(CT)、rs352140 (CT)和rs5743836 (AG)与宫颈癌的发生发展无相关性。2.TLR9基因启动子区rs352139多态性与宫颈癌和癌前病变无明显相关性,与宫颈癌的病理类型、临床分期无关。但是,T等位基因与宫颈癌组织分化有关,携带T等位基因的宫颈癌患者组织分化更好。同时,T/T基因型频率在浅肌层组占优势,而C/T基因型在深肌层组占优势,表明C/T基因型可能增加宫颈癌深肌层浸润的风险,这也提示C/T基因型可能是宫颈癌进展的危险因素,可为宫颈癌的治疗选择及预后评估提供一定的依据。而在淋巴结转移的比较中,携带T等位基因的宫颈癌患者更容易发生转移,C/C基因型频率在无淋巴结转移组占优势,表明C/C基因型可能减少宫颈癌淋巴结转移的风险,为宫颈癌的治疗选择及预后评估提供了一定的遗传学依据。3.TLR9基因启动子区rs352140多态性与宫颈癌和癌前病变无明显相关性,与宫颈癌的病理类型、临床分期、组织分化程度、肌层浸润深度、淋巴结转移无关。4.TLR9基因启动子区rs5743836多态性与宫颈癌和癌前病变无明显相关性,与宫颈癌的病理类型、临床分期、组织分化程度、肌层浸润深度、淋巴结转移无关。
[Abstract]:[Objective] to investigate the promoter region of TLR9 gene single nucleotide polymorphism (SNPs) rs352139 CT, rs352140CT and rs5743836AG and the occurrence and development of cervical cancer. The correlation method according to the principles of "informed consent", select the women of Han population in Yunnan area in 253 cases of patients with cervical cancer, precancerous lesions in 92 cases, 330 cases of normal health examination method, type using TaqMan probe gene were genotyped for the SNP locus, and construct the evaluation of the 3 haplotypes, SNP alleles, correlation. Results the occurrence and development of genotype and haplotype and cervical cancer]1.TLR9 gene promoter SNP locus rs352139 (CT), rs352140 (CT) rs5743836, (AG) difference in the frequency distribution of genotype and allele in each group were not statistically significant (P0.05).2. linkage disequilibrium analysis results showed that: in the cancer group and the control group, rs352139 (CT) and rs57 43836 (AG), rs352140 (CT) and rs5743836 (AG) has strong linkage, D'greater than 0.8.3. based on linkage disequilibrium results rs352139 (CT), rs352140 (CT) and rs5743836 (AG) distribution frequency differences in the cancer group and the control group in the haplotype was not statistically significant (P0.05).4. in cervical cancer group were stratified analysis, the results showed that TLR9 gene rs352139, rs352140 and rs5743836 alleles and genotype frequencies in squamous cell carcinoma and non carcinoma group, between clinical stage and clinical stage II had no significant difference, but the value of P 0.05., the promoter region of TLR9 gene rs352139 allele T the frequency in the well differentiated group was significantly higher than that of poorly differentiated group, there was significant difference between two groups (P=0.029, OR=0.629, 95%CI=[0.414 ~ 0.957]).Rs352139 allele frequency distribution of C in shallow muscle layer and deep muscle layer group with significant difference (P=0.038 X, 2=4.299), the C allele frequency in deep muscle layer group was significantly higher than that of shallow muscle layer (43.8%, 32.7%) of.TLR9 gene promoter rs352139 locus in lymph node metastasis and lymph node metastasis in the comparison of the allele frequencies and genotype frequencies in the two groups of difference there was statistical significance (P=0.006 and P=0.025), the C/C genotype frequency in the group without lymph node metastasis was significantly higher than that in the group with lymph node metastasis (20.3% vs 4.7%). Conclusion]1. in Yunnan Han women, the promoter of TLR9 gene of 3 SNP loci in rs352139 sub area (CT), rs352140 (CT) and rs5743836 (AG) there is no correlation between.2.TLR9 gene promoter rs352139 polymorphism and cervical cancer and precancerous lesions had no significant correlation with the occurrence and development of cervical cancer, and pathological types of cervical cancer, independent of clinical stage. However, T alleles and cervical cancer tissue differentiation, carrying T allele Cervical cancer differentiation better. At the same time, the frequency of T/T genotype in the shallow muscle layer is dominant, and the C/T genotype in the deep muscular layer was dominant, showed that the C/T genotype may increase the risk of cervical cancer in deep myometrial invasion, suggesting that C/T genotype may be a risk factor for the progression of cervical cancer, can to provide a basis for the evaluation of treatment and prognosis of cervical cancer and lymph node metastasis. In comparison, the T allele of cervical cancer patients are more prone to metastasis, C/C genotype frequencies in the group without lymph node metastasis is dominant, showed that the C/C genotype may reduce less risk of cervical cancer with lymph node metastasis that provides the genetic basis for.3.TLR9 gene promoter rs352140 polymorphism and cervical cancer and precancerous lesions had no significant correlation to treatment options and prognosis of cervical cancer and cervical cancer, pathological type, clinical stage, tissue differentiation No correlation was found between the.4.TLR9 gene promoter rs5743836 polymorphism and cervical cancer and precancerous lesion. It was not related to the pathological type, clinical stage, histological differentiation, depth of invasion and lymph node metastasis of cervical cancer.

【学位授予单位】：昆明医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.33

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