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An integrated analysis of the association between Ts gene polymorphisms and clinical outcome in gastric and colorectal cancer patients treated with 5-FU-based regimens
Authors:Ying-Chao Wang  Hui-Ping Xue  Zhen-Hua Wang  Jing-Yuan Fang
Affiliation:1. GI Division, Shanghai Institution of Digestive Disease, School of Medicine, Renji Hospital, Shanghai Jiao-Tong University, Shanghai, 200001, China
2. Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai Jiao-Tong University, 145 Middle Shandong Rd, Shanghai, 200001, China
3. State Key Laboratory of Oncogene and Related Genes, Shanghai Jiao-Tong University, 145 Middle Shandong Rd, Shanghai, 200001, China
Abstract:Thymidylate synthetase is the major target of 5-fluorouracil (5-FU), which is widely used for the treatment of gastric cancer (GC) and colorectal cancer (CRC). This meta-analysis aimed to elucidate the effect of Ts polymorphisms on the efficacy of 5-FU-based chemotherapy in GC and CRC patients. Individual data were analyzed from 10 studies of 1102 GC and CRC patients treated with 5-FU-based regimens. The primary outcomes of interest were overall survival (OS) and progression-free survival (PFS). Data were pooled using the program STATA version 10.0 (Stata Corporation, College Station, TX). The relationship between the Ts polymorphism and survival following 5FU-based treatment of GC and CRC patients was systematically summarized. Compared with the C allele, the G allele was associated with shorter PFS but with similar OS in Caucasian CRC patients. Compared with the 3R/3R genotype, the 2R/3R or 2R/2R genotype was associated with the same PFS, but with a shorter OS, particularly in Caucasian CRC patients. These results show a correlation between survival following 5-FU-based therapy and tumor genotype in Caucasian CRC patients. Larger studies and further clinical trials are required to confirm this observation.
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