發(fā)布時間：2018-04-22 08:32

  本文選題：腦膠質(zhì)瘤 + RAD52�。� 參考：《北京化工大學(xué)》2014年碩士論文

【摘要】：在中樞神經(jīng)系統(tǒng)的癌癥中腦膠質(zhì)瘤占大約80%,預(yù)后較差。我們運用病例-對照研究方法,針對404例腦膠質(zhì)瘤病人和經(jīng)過篩選的性別年齡均匹配的820例正常對照,系統(tǒng)研究了RAD52基因和白細胞端粒長度相關(guān)遺傳變異與腦膠質(zhì)瘤遺傳易感性的相關(guān)關(guān)系。針對DNA修復(fù)基因RAD52,我們對其基因座位中的5個單核苷酸多態(tài)性(single nucleotide polymorphism, SNP) (rs 1051669,rs10774474,rs1 1571378,rs7963551和rs6489769)進行了基因分型。進而,采用logistic回歸分析計算比值比(Odds Ratios,OR值)和95%置信區(qū)間(Confidence Interval, CI),揭示了上述SNP與腦膠質(zhì)瘤發(fā)病風(fēng)險的關(guān)聯(lián)。我們發(fā)現(xiàn),只有RAD52rs7963551 SNP與腦膠質(zhì)瘤的易感性顯著相關(guān)。與攜帶有AA基因型的個體相比,攜帶rs7963551 AC或CC基因型個體的OR值分別為0.49(95%CI=0.37-0.65,P=9.29×10-6)或0.39(95%CI=0.18-0.81,P=0.012)。分層分析顯示,rs7963551 SNP與星形細胞瘤(P=6.3×10-6)或少突星形細胞腫瘤(P=0.002)的發(fā)表風(fēng)險顯著相關(guān)。前人發(fā)現(xiàn)外周血白細胞端粒長度(leukocyte telomere length,LTL)較短與歐洲人群中的某些癌癥發(fā)病風(fēng)險呈現(xiàn)明顯相關(guān)性。同時在歐洲人群中發(fā)現(xiàn),14q21 rs398652以及1p34.2 rs621559兩個SNP與LTL顯著相關(guān)。我們的前期研究顯示,在中國人群中LTL相關(guān)的兩個SNP位點(14q2l rs398652和1p34.2 rs621559)和食管鱗狀細胞癌的發(fā)病風(fēng)險相關(guān)�；诖�,本研究系統(tǒng)揭示了中國北方人群中rs621559和rs398652 SNP與腦膠質(zhì)瘤遺傳易感性的關(guān)系。我們以404例腦膠質(zhì)瘤以及820例正常對照樣本為研究對象,對14q2l rs398652和1p34.2 rs621559兩個SNP進行基因分型。我們發(fā)現(xiàn),具有1p34.2rs621559 AG或GG基因大]型的受試者其OR值為1.82(95%CI=1.07-3.09,P=0.026)或2.12(95%CI=1.26-3.56,P=0.005),與具有rs621559 AA基因型的受試者相比更易罹患腦膠質(zhì)瘤。類似地,與14q21 rs398652 AA基因型相比,AG或GG基因型(OR=1.39,957石CI=1.07-1.80,P=0.012;OR=1.52,95%CI=1.04-2.20,P=0.029)顯著增加腦膠質(zhì)瘤患病風(fēng)險。我們的研究結(jié)果首次鑒定了中國人群中腦膠質(zhì)瘤發(fā)病風(fēng)險相關(guān)的RAD52 rs7963551多態(tài)性以及LTL相關(guān)的兩個遺傳多態(tài)rs621559和rs398652。
[Abstract]:Gliomas account for about 80 percent of cancer in the central nervous system, with poor prognosis. We used a case-control study to study 404 glioma patients and 820 normal controls who were matched by sex and age. The relationship between genetic variation of RAD52 gene and leukocyte telomere length and genetic susceptibility to glioma was systematically studied. For the DNA repair gene RAD52, we genotyped five single nucleotide polymorphisms (SNPs) rs1051669, rs10774474, rs1 1571378, rs7963551 and rs64897669 in its locus. Furthermore, logistic regression analysis was used to calculate odds ratio odds ratio (OR) and 95% confidence interval (95% confidence interval), which revealed the association between the above SNP and the risk of glioma. We found that only RAD52rs7963551 SNP was significantly associated with glioma susceptibility. Compared with individuals with AA genotype, the OR values of individuals with rs7963551 AC or CC genotype were 0.4995, 0.37-0.65P9.29 脳 10 ~ (-6) or 0.3995% ~ 0.18-0.81C ~ (0.012), respectively. Stratified analysis showed that rs7963551 SNP was significantly associated with the published risk of astrocytoma (6. 3 脳 10-6) or oligodendroid astrocytoma (P0. 002). It was found that the shorter leukocyte telomere length in peripheral blood leukocytes was associated with the risk of some cancers in European population. At the same time, there was a significant correlation between SNP 14q21 rs398652 and 1p34.2 rs621559 and LTL in European population. Our previous study showed that two SNP loci associated with LTL were associated with the risk of esophageal squamous cell carcinoma in Chinese population (14q2l rs398652 and 1p34.2 rs621559). Based on these results, this study revealed the relationship between rs621559 and rs398652 SNP and genetic susceptibility to glioma in northern China. 14q2l rs398652 and 1p34.2 rs621559 were genotyped from 404 gliomas and 820 normal controls. We found that the OR of the subjects with 1p34.2rs621559 AG or GG gene] genotype was 1.82 ~ 95) or 2.12 ~ 95% ~ 1.26 ~ 3.09% P0. 026) or 2.12 ~ 95% CI = 1.26 ~ 56 ~ (6) P ~ (0.005), which was more likely to develop glioma than those with rs621559 AA genotype. Similarly, compared with the 14q21 rs398652 AA genotype, the AG or GG genotype OR1.39957 increased the risk of glioma significantly. Our results were the first to identify the RAD52 rs7963551 polymorphism associated with the risk of glioma in Chinese population, and two genetic polymorphisms associated with LTL, rs621559 and rs398652.
【學(xué)位授予單位】：北京化工大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R739.41

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