本文關(guān)鍵詞： Toll樣受體9 宮頸癌 發(fā)生發(fā)展 單核苷酸多態(tài)性 相關(guān)性　出處：《昆明醫(yī)科大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：[目的]探討TLR9基因啟動子區(qū)單核苷酸多態(tài)性位點(diǎn)(SNPs) rs352139 CT、rs352140CT和rs5743836AG與宮頸癌發(fā)生發(fā)展的相關(guān)性。[方法]根據(jù)“知情同意”原則,選取云南地區(qū)漢族女性人群中宮頸癌患者253例,癌前病變患者92例,正常健康體檢者330例,采用TaqMan探針基因分型的方法對上述SNP位點(diǎn)進(jìn)行基因分型,并構(gòu)建單倍型,評估上述3個SNP位點(diǎn)的等位基因、基因型以及單倍型與宮頸癌發(fā)生發(fā)展的相關(guān)性。[結(jié)果]1.TLR9 基因啟動子區(qū) SNP 位點(diǎn) rs352139(CT)、rs352140(CT)、rs5743836(AG)的基因型和等位基因在各組間的分布頻率差異均無統(tǒng)計(jì)學(xué)意義(P0.05)。2.連鎖不平衡分析結(jié)果顯示:在癌癥組和對照組中,rs352139 (CT)與rs5743836 (AG),rs352140 (CT)與 rs5743836 (AG)間存在強(qiáng)連鎖,D'值大于0.8。3.根據(jù)連鎖不平衡結(jié)果構(gòu)建的rs352139 (CT)、rs352140 (CT)和rs5743836(AG)的單倍型在癌癥組和對照組中的分布頻率差異無統(tǒng)計(jì)學(xué)意義(P0.05)。4.對宮頸癌組進(jìn)行分層分析,研究結(jié)果顯示TLR9基因rs352139、rs352140和rs5743836位點(diǎn)等位基因、基因型頻率在鱗癌組與非鱗癌組、臨床Ⅰ期與臨床Ⅱ期之間比較無統(tǒng)計(jì)學(xué)差異,P值0.05。但是,TLR9基因啟動子區(qū)rs352139等位基因T的頻率在分化好組顯著高于分化差組,兩組比較差異有統(tǒng)計(jì)學(xué)意義(P=0.029, OR=0.629 95%CI=[0.414～0.957])。rs352139 位點(diǎn)等位基因 C 的頻率在淺肌層組和深肌層組中分布具有顯著差異性(P=0.038, χ2=4.299),其中等位基因C的頻率在深肌層組明顯高于淺肌層組(43.8%、32.7%)。TLR9基因啟動子區(qū)rs352139位點(diǎn)在有淋巴結(jié)轉(zhuǎn)移和無淋巴結(jié)轉(zhuǎn)移的比較中,等位基因頻率和基因型頻率在兩組比較中差異有統(tǒng)計(jì)學(xué)意義(P=0.006和P=0.025),其中C/C基因型頻率在無淋巴結(jié)轉(zhuǎn)移組明顯高于有淋巴結(jié)轉(zhuǎn)移組(20.3% vs 4.7%)。[結(jié)論]1.在云南漢族女性群體中,TLR9基因啟動子區(qū)的3個SNP位點(diǎn)rs352139(CT)、rs352140 (CT)和rs5743836 (AG)與宮頸癌的發(fā)生發(fā)展無相關(guān)性。2.TLR9基因啟動子區(qū)rs352139多態(tài)性與宮頸癌和癌前病變無明顯相關(guān)性,與宮頸癌的病理類型、臨床分期無關(guān)。但是,T等位基因與宮頸癌組織分化有關(guān),攜帶T等位基因的宮頸癌患者組織分化更好。同時,T/T基因型頻率在淺肌層組占優(yōu)勢,而C/T基因型在深肌層組占優(yōu)勢,表明C/T基因型可能增加宮頸癌深肌層浸潤的風(fēng)險,這也提示C/T基因型可能是宮頸癌進(jìn)展的危險因素,可為宮頸癌的治療選擇及預(yù)后評估提供一定的依據(jù)。而在淋巴結(jié)轉(zhuǎn)移的比較中,攜帶T等位基因的宮頸癌患者更容易發(fā)生轉(zhuǎn)移,C/C基因型頻率在無淋巴結(jié)轉(zhuǎn)移組占優(yōu)勢,表明C/C基因型可能減少宮頸癌淋巴結(jié)轉(zhuǎn)移的風(fēng)險,為宮頸癌的治療選擇及預(yù)后評估提供了一定的遺傳學(xué)依據(jù)。3.TLR9基因啟動子區(qū)rs352140多態(tài)性與宮頸癌和癌前病變無明顯相關(guān)性,與宮頸癌的病理類型、臨床分期、組織分化程度、肌層浸潤深度、淋巴結(jié)轉(zhuǎn)移無關(guān)。4.TLR9基因啟動子區(qū)rs5743836多態(tài)性與宮頸癌和癌前病變無明顯相關(guān)性,與宮頸癌的病理類型、臨床分期、組織分化程度、肌層浸潤深度、淋巴結(jié)轉(zhuǎn)移無關(guān)。
[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.

【學(xué)位授予單位】：昆明醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R737.33

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本文編號：1515693