Dissertation > Excellent graduate degree dissertation topics show

XRCC1, ADPRT gene polymorphism and TS gene expression and malignant tumor chemosensitivity relationship experiments and evidence-based medical research

Author: QiuLiXin
Tutor: QianXiaoPing；LiuBaoRui
School: Nanjing Medical University
Course: Oncology
Keywords: XRCC1 ADPRT Gene polymorphism Non - small cell lung cancer Platinum drugs Chemosensitivity Thymidylate synthase Advanced colorectal cancer Fluorouracil Meta-analysis
CLC: R734.2
Type: Master's thesis
Year: 2009
Downloads: 76
Quote: 0
Read: Download Dissertation

Abstract

The first part XRCC1 and ADPRT gene polymorphism with advanced non-small cell lung cancer platinum-based chemotherapy sensitivity study [Abstract] Objective: To investigate the DNA base excision repair pathway XRCC1 T-77C, Argl94Trp, Arg399Gln and the ADPRT Val762Ala genes attitude with advanced non-small cell lung cancer (NSCLC) platinum-based chemotherapy sensitivity associated and joint analysis of four single nucleotide polymorphisms predict the effect of platinum-based chemotherapy. Methods: pathologically-confirmed 107 cases accept platinum drug-based chemotherapy in patients with advanced NSCLC, extracted from peripheral blood DNA detected by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) Genotype analysis of each genotype efficiency associated with platinum-based chemotherapy, and non-conditional logistic regression model corrected for age, gender, histological type, clinical stage, and treatment programs. Results: Multivariate analysis XRCC1 T-77C polymorphism found to carry at least one C allele in patients with platinum-based chemotherapy the efficient carrying the wild type by 1.41-fold (95% CI: 0.51-3.93 ). Carried the XRCC1 Argl94Trp polymorphism multivariate analysis found carrying Arg / Trp genotype in patients with platinum-based chemotherapy efficient Arg / Arg genotype were 3.61 times (95% CI: 1.36-9.63); carry at least chemotherapy in patients with a Trp allele efficient carrying the Arg / Arg genotype by 3.52-fold (95% CI: 1.36-9.11), and the differences were statistically significant. XRCC1 Arg399Gln polymorphism univariate analysis, found to be in possession of at least one Gln allele in patients with chemotherapy the efficient carrying Arg / Arg genotype had a 0.42-fold (95% CI: 0.19 to 0.93), difference statistically significant; multi-factor correction found to be in possession of at least one Gln allele in patients with chemotherapy the efficient carrying Arg / Arg genotype had a 0.52-fold (95% CI: 0.22-1.26), but the difference was no longer has statistically significant. Multivariate analysis of the ADPRT Val762Ala polymorphism, it is found to be in possession of at least one Ala allele in patients with chemotherapy efficient carrying the Val / Val genotype were 1.57 times (95% CI: 0.67 - 3.66). Joint analysis of the total number of platinum drugs each patient four polymorphic sites sensitive genotype efficiency associated with platinum-based chemotherapy, corrected by multivariate analysis, it is found to carry a 3-4 platinum drug sensitivity gene efficient type of chemotherapy in patients with 0-2 platinum-based drug-sensitive genotype 4.15-fold (95% CI: 1.54-11.19), a statistically significant difference; carry 5-6 platinum drug-sensitive genotype patients with chemotherapy efficiency with 0-2 platinum-based drug-sensitive genotype were 2.92 times (95% CI: 0.60-14.23). Conclusions: XRCC1 Argl94Trp polymorphism with advanced NSCLC platinum drug chemosensitivity correlation, Trp allele carriers are more sensitive to platinum-based chemotherapy; XRCC1 Arg399Gln polymorphism with platinum-based chemotherapy sensitivity relationship needs to be further confirmed. seemed to be carrying the wild-type Arg / Arg is more sensitive to platinum-based chemotherapy; XRCC1 T-77C polymorphism but failed to find, the ADPRT Val762Ala polymorphism with platinum-based chemotherapy sensitivity significantly associated; 4 polymorphism loci joint prediction performance than single locus analysis. Abstract Objective: published on the expression of thymidylate synthase (TS) status with advanced colorectal cancer fluorouracil second part of TS gene expression with advanced colorectal cancer fluoropyrimidine chemotherapy sensitivity: Meta analysis based on 24 studies class of chemotherapy sensitivity study results are inconsistent, for a more systematic and comprehensive assessment of the association between the two, Meta-analysis of these original research? methods: by searching PubMed and Embase databases collected in line with the standard literature, Inclusion criteria were: (1) with advanced colorectal cancer patients; (2) received treatment with fluorouracil; (3) evaluation of TS expression status and treatment of the relationship between efficiency? pooled analysis of the relative odds ratio (RR) and its 95 % confidence interval (95% CI) to assess TS expression status of efficiency associated with chemotherapy, and in accordance with the specimens drawn from different parts and TS expression detection methods performed a subgroup analysis? Results: A total of 24 studies of a total of 1112 cases were included in the Meta analysis? summary of all studies RR of 2.20 (95% CI ,1.82-2 .66; P = 0.000)? subgroup analysis of the specimen material positions, when specimens from metastases, RR = 3.23 (95% CI, 2.27 -4.59; P = 0.000); When specimens based on the primary tumor RR was 1.89 (95% CI, 1.45 - 2 .48; P = 0.000).? Then, we performed a subgroup analysis according to the different methods of detection of TS expression by immunofluorescence histochemistry (IHC) detection subgroup RR was 1.83 (95% CI ,1.44-2 .34; P = 0.000); subgroup was detected by RT-PCR RR was 2.96 (95% CI, 2.07 - 4 .22; P = 0.000)? Conclusion: In summary the results showed that the TS low expression in patients with advanced colorectal cancer fluorouracil-based chemotherapy is more sensitive? subgroup analysis showed that, regardless of the specimens from metastases or primary tumor are prompted TS low expression tumor fluorouracil-based chemotherapy is more sensitive, but for the late transfer of patients to detect metastases TS expression status can be more sensitive to predict efficacy; both RT-PCR and IHC detection method can detect patients with TS low expression fluorouracil-based chemotherapy is more sensitive RT-PCR method is more sensitive than the IHC method to predict the efficacy of?

XRCC1, ADPRT gene polymorphism and TS gene expression and malignant tumor chemosensitivity relationship experiments and evidence-based medical research

Abstract

Related Dissertations