本文選題：喉腫瘤 + 單核苷酸多態(tài)性��； 參考：《天津醫(yī)科大學(xué)》2011年碩士論文

【摘要】：目的 檢測]Pinl (peptidyl-prolyl cis/trans isomerase 1)啟動子區(qū)域和內(nèi)含子區(qū)域的單核苷酸多態(tài)性(single nucleotide polymorphism, SNP)位點rs2233678、rs2233679和rs2287838在喉鱗狀細胞癌(laryngeal squamous cell carcinoma, LSCC)患者及其對照組人群外周血中的基因型頻率和等位基因型頻率。比較上述多態(tài)性位點基因型頻率和等位基因型頻率在兩組中的差異,分析其分布頻率與不同臨床參數(shù)(如頸部淋巴結(jié)轉(zhuǎn)移及臨床分期)的關(guān)系。旨在尋求具有重要臨床意義的診斷指標(biāo)和治療靶點,明確它們和LSCC發(fā)生發(fā)展的關(guān)系,為LSCC早期的基因型診斷以及靶向治療提供科學(xué)依據(jù)。 方法 采用聚合酶鏈?zhǔn)椒磻?yīng)-限制性內(nèi)切酶片段長度多態(tài)性(polymerase chain reaction-restriction fragment length polymorphism, PCR-RFLP)方法檢測LSCC患者以及非癌癥對照組人群外周血中Pin1基因相關(guān)的SNP位點,即rs2233678、rs2233679和rs2287838(其中rs2233678和rs2233679兩個位點位于Pin1基因的啟動子區(qū)域,rs2287838位點位于Pin1基因的內(nèi)含子區(qū)域)的單核苷酸多態(tài)性在兩組中的差異；并比較突變位點的基因型頻率以及等位基因型頻率與患者頸部淋巴結(jié)轉(zhuǎn)移、臨床分期間的關(guān)系。應(yīng)用SPSS16.0統(tǒng)計學(xué)軟件對實驗數(shù)據(jù)進行分析。應(yīng)用擬合優(yōu)度χ2檢驗對對照組基因型頻率分布行Hardy-Weinberg平衡分析；病例組與對照組基因型和等位基因型頻率分布比較用χ2檢驗,以比值比(odds ratio, OR)及其95%可信區(qū)間(confidence interval, CI)來表示基因型之間的相對風(fēng)險度。P0.05作為差異有統(tǒng)計學(xué)意義的標(biāo)準(zhǔn)。 結(jié)果 1.對照組人群三個位點分別經(jīng)過Hardy-Weinberg遺傳平衡檢驗,P0.05,符合Hardy-Weinberg遺傳平衡定律,具有群體代表性。 2.rs2233678多態(tài)性位點的基因型頻率分布在病例組和對照組中差別有明顯統(tǒng)計學(xué)意義(P=0.004)。對其臨床參數(shù)分組分別進行統(tǒng)計學(xué)分析發(fā)現(xiàn)其基因型頻率分布在淋巴結(jié)轉(zhuǎn)移、TNM臨床分期分組中差別無統(tǒng)計學(xué)意義。進一步對其基因型進行相對風(fēng)險度分析,GG基因型發(fā)生喉鱗癌的危險性是GC+CC基因型的3.821倍(P=0.001, OR=3.821,95%CI=1.632-8.948); G等位基因突變的喉鱗癌發(fā)病風(fēng)險性是C等位基因型的3.858倍(P=0.001, OR=3.858, 95%CI=1.716-8.673). 3.rs2233679多態(tài)性位點的基因型頻率分布在病例組和對照組中差別無明顯統(tǒng)計學(xué)意義(P=0.207)。 4.rs2287838多態(tài)性位點的基因型頻率分布在病例組和對照組中差別有明顯統(tǒng)計學(xué)意義(P=0.000)。對其臨床參數(shù)分組分別進行統(tǒng)計學(xué)分析rs2287838多態(tài)性位點的基因型頻率分布在淋巴結(jié)轉(zhuǎn)移、TNM臨床分期分組中差別無統(tǒng)計學(xué)意義。進一步對其基因型進行相對風(fēng)險度分析,以rs2287838 TT基因型為參照,CT基因型發(fā)生喉鱗癌的危險性是TT基因型的0.141倍(P=0.000, OR=0.141, 95%CI=0.060-0.330); CC基因型是TT基因型發(fā)生喉鱗癌風(fēng)險性的0.323倍(P=0.012, OR=0.323,95%CI=0.131-0.796)。T等位基因突變的喉鱗癌易感性是C等位基因突變的1.470倍(p=0.059, OR=1.470,95%CI=0.985-2.193),但是差別處于臨界值,未達到統(tǒng)計學(xué)意義。 結(jié)論 1.rs2233678多態(tài)性位點與喉鱗狀細胞癌易感性有關(guān)。但是rs2233678位點基因型突變不參與喉鱗癌的淋巴結(jié)轉(zhuǎn)移以及惡性進展。G等位基因突變與喉癌的發(fā)病有關(guān),促進喉鱗癌的發(fā)生。 2.rs2233679多態(tài)性位點與喉鱗狀細胞癌易感性無相關(guān)性。 3.rs2287838多態(tài)性位點與喉鱗狀細胞癌易感性有關(guān)。TT基因型與喉鱗癌的易感性有關(guān),促進喉鱗癌的發(fā)生。但是rs2287838位點基因型突變不參與喉鱗癌的淋巴結(jié)轉(zhuǎn)移以及惡性進展。
[Abstract]:objective
Detection of genotype frequency in peripheral blood of]Pinl (peptidyl-prolyl cis/trans isomerase 1) single nucleotide polymorphisms (single nucleotide polymorphism, SNP) loci in the promoter region and intron region of the peripheral blood of the laryngeal squamous cell carcinoma and the control group. The differences in genotype frequency and allele frequency in the two groups were compared. The relationship between the frequency of the polymorphic loci and the allele frequency in the two groups was analyzed. The relationship between the frequency of the distribution and the different clinical parameters, such as the cervical lymph node metastasis and the clinical stage, was analyzed. The purpose was to find the diagnostic indicators and therapeutic targets with important clinical significance, and to clarify their and LSCC hair. The relationship between growth and development provides a scientific basis for early diagnosis and targeted therapy of LSCC.
Method
The polymerase chain reaction restriction endonuclease fragment length polymorphism (polymerase chain reaction-restriction fragment length polymorphism, PCR-RFLP) was used to detect the Pin1 gene related SNP loci in peripheral blood of patients with LSCC and non cancer control groups. 9 the two loci are located in the promoter region of the Pin1 gene and the difference in the single nucleotide polymorphism of the rs2287838 loci in the intron of the Pin1 gene. The relationship between the genotype frequency of the mutation site and the allele frequency of the allele with the cervical lymph node metastasis and the clinical staging is applied. The SPSS16.0 statistics software is used. The analysis of experimental data was carried out. Hardy-Weinberg balance analysis was applied to the genotype frequency distribution of the control group by using the goodness of fit chi 2 test. The genotype and allele frequency distribution of the case group and the control group were compared with the x 2 test, and the ratio Ratio (odds ratio, OR) and the 95% credible region (confidence interval, CI) were used to express the genotype between the two groups. The relative risk.P0.05 was statistically significant.
Result
1. the three locus of the control group were tested by Hardy-Weinberg genetic equilibrium, P0.05, which was in line with the Hardy-Weinberg genetic balance law.
The genotype frequency distribution of 2.rs2233678 polymorphic loci was significantly different in the case group and the control group (P=0.004). The statistical analysis of its clinical parameters found that the frequency distribution of the genotype was in the lymph node metastasis, and there was no statistical significance in the TNM clinical staging group. For the risk analysis, the risk of GG genotypes in laryngeal squamous cell carcinoma is 3.821 times the GC+CC genotype (P=0.001, OR=3.821,95%CI=1.632-8.948), and the risk of laryngeal squamous cell carcinoma with G allele mutation is 3.858 times as much as C allele (P=0.001, OR=3.858, 95%CI=1.716-8.673).
There was no significant difference in genotype frequency distribution between 3.rs2233679 and polymorphic loci in case group and control group (P=0.207).
The genotype frequency distribution of 4.rs2287838 polymorphic loci was significant (P=0.000) in the case group and the control group (P=0.000). The genotype frequency distribution of the rs2287838 polymorphic loci was statistically analyzed in the lymph node metastasis, and the difference was not statistically significant in the TNM clinical subdivision. The genotype was analyzed with the relative risk degree, with the rs2287838 TT genotype as the reference. The risk of CT genotype of laryngeal squamous cell carcinoma was 0.141 times the TT genotype (P=0.000, OR=0.141, 95%CI=0.060-0.330), and CC genotypes were 0.323 times of the risk of laryngeal squamous cell carcinoma in the TT genotype (P= 0.012, OR=0.323,95%CI=0.131-0.796) gene mutation of the allele. The susceptibility of squamous cell carcinoma was 1.470 times that of the C allele (p=0.059, OR=1.470,95%CI=0.985-2.193), but the difference was at a critical value, and did not reach statistical significance.
conclusion
1.rs2233678 polymorphic loci are associated with susceptibility to laryngeal squamous cell carcinoma. However, the mutation of the rs2233678 loci is not involved in the lymph node metastasis of laryngeal squamous cell carcinoma and the mutation of the malignant progression.G allele is associated with the incidence of larynx cancer, which promotes the occurrence of laryngeal squamous cell carcinoma.
There was no correlation between 2.rs2233679 polymorphisms and susceptibility to laryngeal squamous cell carcinoma.
3.rs2287838 polymorphic loci are associated with susceptibility to laryngeal squamous cell carcinoma and the.TT genotype is associated with susceptibility to laryngeal squamous cell carcinoma, promoting the occurrence of laryngeal squamous cell carcinoma, but the genotype mutation at the rs2287838 site does not participate in the lymph node metastasis and malignant progression of laryngeal squamous cell carcinoma.

【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2011
【分類號】：R739.65

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