| ABCB1、RPA1基因多态性与奥沙利铂治疗胃癌的疗效和不良反应的相关性研究 | |
| Alternative Title | ASSOCIATION OF ABCB1 AND RPA1 GENE POLYMORPHISMS WITH EFFICACY AND ADVERSE REACTIONS OF OXALIPLATIN IN GASTRIC CANCER |
| 杨文娟 | |
| Subtype | 硕士 |
| Thesis Advisor | 刘欣跃 |
| 2021-05-26 | |
| Degree Grantor | 兰州大学 |
| Place of Conferral | 兰州 |
| Degree Name | 医学硕士 |
| Degree Discipline | 临床检验诊断学 |
| Keyword | 胃癌 奥沙利铂 单核苷酸多态性 疗效 药物不良反应 |
| Abstract | 目的：明确甘肃省部分胃癌患者ABCB1 rs1045642、rs1128503、rs2032582和RPA1 rs5030740位点的分布情况，探索单核苷酸多态性（Single nucleotide polymorphisms，SNPs）与奥沙利铂治疗胃癌的疗效、不良反应之间的相关性，预测SNPs在临床应用中的价值。 方法：本研究共纳入189例奥沙利铂治疗的胃癌患者，收集性别、年龄、民族、肿瘤部位等临床病理特征。采用等位基因特异性聚合酶链式反应（AS-PCR）对所纳入人群外周血基因组DNA中ABCB1 rs1045642进行基因分型;直接测序法对ABCB1 rs1128503、rs2032582和RPA1 rs5030740进行基因分型。最后，使用logistic回归分析SNPs与奥沙利铂治疗胃癌患者的客观缓解率（ORR）、疾病控制率（DCR）、不良反应的相关性;使用Cox回归分析SNPs与奥沙利铂治疗胃癌患者的无进展生存时间（progression-free survival，PFS）的相关性。 结果：（1）ABCB1 rs1045642位点CC、CT、TT基因型频率分别为40.2%、42.9%、16.9%;ABCB1 rs1128503位点CC、CT、TT基因型频率分别为10.5%、50.3%、39.25%;ABCB1 rs2032582位点GG、GT、GA、AA、TT、AT基因型频率分别为22.7%、32.3%、12.7%、2.1%、20.1%和10.1%;RPA1 rs5030740位点TT、TC、CC基因型频率分别为62.4%、32.3%、5.3%。（2）在ABCB1 rs2032582共显性模型中，GA基因型患者的DCR较GG基因型差（GA vs GG：OR=0.216，95%CI=0.052-0.904，P=0.036）。（3）ABCB1 rs1045642位点TT基因型发生III级胃肠道不良反应的风险是CT+CC基因型患者的5.543倍（OR=5.543，95%CI=1.159-26.501，P=0.032）;TCG单倍型患者出现III级血液学不良反应的风险是I-II级血液学不良反应的5.134倍（OR=5.134,95%CI=1.273-20.706，P=0.011）;（4）RPA1 rs5030740位点CC基因型患者较TT或TT+TC基因型患者的PFS短（HR=12.295，95%CI=2.538-59.567，P=0.002;HR=9.449，95%CI=2.038-43.816，P=0.004）。此外，RPA1 rs5030740患者TT基因型的PFS较TC+CC基因型患者长（HR=2.948，95%CI=1.169-7.434，P=0.022）。 结论：（1）ABCB1 rs2032582位点GA基因型较GG基因型更容易出现疾病进展;（2）ABCB1 rs1045642位点隐性模型与化疗后胃肠道不良反应具有相关性;TCG单倍型出现III级血液学不良反应的风险高于I-II级血液学不良反应;（3）RPA1 rs5030740位点是PFS的独立预后因素。 |
| Other Abstract | Objective: The distributions of ABCB1 rs1045642, rs1128503, rs2032582 and RPA1 rs5030740 were determined in some patients with gastric cancer in Gansu Province. To investigate whether there were associations between Single nucleotide polymorphisms (SNPs) and efficacy or adverse reactions of oxaliplatin-based chemotherapy for gastric cancer, and to predict the value of SNPs in clinical application. Methods: In this study, 189 patients with gastric cancer receiving oxaliplatin-based chemotherapy were included. We collected the clinical and pathological characteristics of patients, such as gender, age, ethnicity, tumor location, etc. ABCB1 rs1045642 was genotyped by allele specific PCR (AS-PCR). ABCB1 rs1128503, rs2032582 and RPA1 rs5030740 were genotyped by direct sequencing. Finally, we used logistic regression to evaluate the association between SNPs and objective response rate (ORR) or disease control rate (DCR) or adverse reactions of receiving oxaliplatin-based chemotherapy in patients with gastric cancer. Logistic regression was used to analyze the association between SNPs and progression-free survival (PFS) of receiving oxaliplatin-based chemotherapy in patients with gastric cancer. Results: (1) In ABCB1 rs1045642, the genotype frequencies of CC, CT and TT were 40.2%, 42.9% and 16.9%, respectively. The genotype frequencies of CC, CT and TT in ABCB1 rs1128503 were 10.5%, 50.3% and 39.25%, respectively. The genotype frequencies of GG, GT, GA, AA, TT and AT in ABCB1 rs2032582 were 22.7%, 32.3%, 12.7%, 2.1%, 20.1% and 10.1%, respectively. The genotype frequencies of TT, TC and CC in RPA1 rs5030740 were 62.4%, 32.3% and 5.3%, respectively. (2) In the codominant model of ABCB1 rs2032582, the DCR of GA carriers was worse than that of GG carriers (GA vs GG: OR=0.216, 95%CI=0.052-0.904, P= 0.036). (3) In ABCB1 rs2032582, the risk of grade III gastrointestinal toxicity in patients with TT was 5.543 times than that of CT+CC carriers (OR=5.543, 95%CI=1.159-26.501, P=0.032);The risk of grade III hematological toxicity in patients with TCG haplotype was 5.134 times than that of grade I-II hematological toxicity (HR=22.528, 95%CI=3.799-133.579, P=0.001;HR=19.447, 95CI%=3.393-111.464, P=0.001). (4) In RPA1 rs5030740, patients with CC had shorter PFS than TT or TT+TC carriers (HR=12.295, 95%CI=2.538-59.567, P=0.002;HR=9.449, 95%CI=2.038-43.816, P=0.004). In addition, in RPA1 rs5030740, patients with TT had longer PFS than that of TC+CC carriers (HR=2.948, 95%CI=1.169-7.434, P=0.022). Conclusions: (1) In ABCB1 rs2032582, GA genotype was more prone to disease progression than GG genotype;(2) In the recessive model, ABCB1 rs1045642 is associated with gastrointestinal toxicity in gastric cancer treated with oxaliplatin. In TCG haplotype, the risk of grade III hematological toxicity was higher than that of grade I-II hematological toxicity;(3) The RPA1 rs5030740 is an independent prognostic factor for PFS. |
| Pages | 72 |
| URL | 查看原文 |
| Language | 中文 |
| Document Type | 学位论文 |
| Identifier | https://ir.lzu.edu.cn/handle/262010/462491 |
| Collection | 第二临床医学院 |
| Affiliation | 第二临床医学院 |
| First Author Affilication | Second Clinical School |
| Recommended Citation GB/T 7714 | 杨文娟. ABCB1、RPA1基因多态性与奥沙利铂治疗胃癌的疗效和不良反应的相关性研究[D]. 兰州. 兰州大学,2021. |
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