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Association of Antioxidative Enzymes Polymorphisms with Efficacy of Platin and Fluorouracil-Based Adjuvant Therapy in Gastric Cancer

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机构: [1]Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, [2]Department of Oncology, Taizhou People’s Hospital, Taizhou, [3]Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, [4]Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, [5]Department of Surgery, Yixing Cancer Hospital, Yixing, [6]Department of Surgery, Yixing People’s Hospital, Yixing, [7]Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, [8]Nanjing Maternity and Child Health Care Institute, The Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing, China
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关键词: Gastric cancer Adjuvant chemotherapy Genetic polymorphism Biomarker

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Background/Aims: Imbalance of oxidative/antioxidative enzymes in cells is associated with carcinogenesis and cancer cell chemoresistance. The aim of this study was to examine the clinical significance of potentially functional single nucleotides polymorphisms (SNPs) in antioxidative enzymes, GPxs and CAT, in stages II and III gastric cancer patients. Methods: A total of 591 gastric cancer patients who had radical gastrectomy were recruited. 207 patients received platinum and fluorouracil-based (PF-based) adjuvant chemotherapy and 384 patients were untreated. GPx1 rs1050450, GPx2 rs4902346, GPx3 rs736775, rs3828599 and CAT rs769218 were genotyped in the DNA samples extracted from paraffin- embedded tumor tissue. Results: CAT rs769218 was significantly correlated with the overall survival (OS) in the dominant model (P = 0.014). Multivariate analysis revealed that CAT rs769218 GA/AA (HR, 0.715; 95% CI, 0.562-0.910, P = 0.006) was an independent prognostic marker indicating improved survival. After adjustments, GPx3 rs736775 TC/CC was significantly associated with improved OS (HR, 0.621; 95% CI, 0.399-0.965; P=0.034) in patients treated with PF-based adjuvant chemotherapy, and CAT rs769218 GA/AA was significantly associated with improved OS (HR, 0.646; 95% CI, 0.482-0.864; P = 0.003) in the untreated patients. PF- based chemotherapy significantly decreased risk of death for patients carrying GPx3 rs736775 TC/CC and age <= 60 years or with diffused type adenocarcinoma compared to surgery alone. Conclusion: our findings suggested CAT rs769218 and GPx3 rs736775 may be considered as prognostic markers in gastric cancer. Patient stratification by GPx3 rs736775 and conventional pathological parameters may provide additional predictive information in treatment decision-making. (C) 2018 The Author(s) Published by S. Karger AG, Basel

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出版当年[2017]版:
大类 | 2 区 生物
小类 | 2 区 生理学 3 区 细胞生物学
最新[2025]版:
大类 | 4 区 生物学
小类 | 4 区 细胞生物学 4 区 生理学
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Q1 PHYSIOLOGY Q2 CELL BIOLOGY
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Q3 PHYSIOLOGY Q4 CELL BIOLOGY

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第一作者机构: [1]Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, [2]Department of Oncology, Taizhou People’s Hospital, Taizhou, [3]Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing,
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通讯机构: [1]Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, [3]Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, [8]Nanjing Maternity and Child Health Care Institute, The Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing, China [*1]Dept. of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine Shanghai [*2]Nanjing Maternity and Child Health Care Hospital, Nanjing (China)
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