title: 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.
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.
authors: GI Division, Shanghai Institution of Digestive Disease, School of Medicine, Renji Hospital, Shanghai Jiao-Tong University, Shanghai, 200001, China.
authors: Ying-Chao
authors: YC
authors: Wang
authors: Hui-Ping
authors: HP
authors: Xue
authors: Zhen-Hua
authors: ZH
authors: Wang
authors: Jing-Yuan
authors: JY
authors: Fang
mesh_terms: D000483:Alleles; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D005006:Ethnicity / Q000235:genetics; D005472:Fluorouracil / Q000008:administration & dosage; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D011110:Polymorphism, Genetic; D011379:Prognosis; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D013940:Thymidylate Synthase / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D013940:Thymidylate Synthase; D005472:Fluorouracil
references: J Surg Oncol. 2010 Jan 1;101(1):22-7
references: 19798689
references: J Clin Oncol. 2004 Feb 1;22(3):529-36
references: 14752076
references: Int J Oncol. 2009 Jan;34(1):219-29
references: 19082493
references: Clin Cancer Res. 2008 Feb 1;14(3):817-25
references: 18245544
references: Int J Colorectal Dis. 2002 Jan;17(1):46-9
references: 12018454
references: J Clin Oncol. 2005 Oct 1;23(28):7230-1; author reply 7231
references: 16192610
references: Pharmacol Res. 2011 Sep;64(3):242-8
references: 21536130
references: Biochem Biophys Res Commun. 1981 Sep 30;102(2):654-8
references: 6458299
references: Pharmacogenomics. 2011 Sep;12(9):1257-67
references: 21919605
references: Clin Cancer Res. 2003 Sep 1;9(10 Pt 1):3700-4
references: 14506161
references: Oncol Rep. 2010 May;23(5):1393-400
references: 20372856
references: Nature. 1957 Mar 30;179(4561):663-6
references: 13418758
references: Pharmacogenet Genomics. 2008 Feb;18(2):161-8
references: 18192902
references: Pharmacogenomics J. 2001;1(1):65-70
references: 11913730
references: Int J Surg Pathol. 2009 Jun;17(3):181-6
references: 19147506
references: J Dig Dis. 2009 May;10(2):118-23
references: 19426394
references: Anal Cell Pathol (Amst). 2010;33(1):1-11
references: 20966539
references: Clin Cancer Res. 2011 Jun 1;17(11):3822-9
references: 21471424
references: Br J Cancer. 2009 May 19;100(10):1549-57
references: 19384296
references: Clin Cancer Res. 2004 Jan 15;10(2):433-9
references: 14760062
references: Pharmacogenet Genomics. 2005 Oct;15(10):723-30
references: 16141798
references: Trials. 2007 Jun 07;8:16
references: 17555582
references: Oncol Rep. 2006 Nov;16(5):1111-5
references: 17016601
references: J Clin Oncol. 2005 Mar 1;23(7):1365-9
references: 15735113
references: J Biol Chem. 1981 Sep 10;256(17):8885-8
references: 6455432
references: J Surg Oncol. 2009 Dec 1;100(7):546-52
references: 19722231
references: Oncol Rep. 2007 Jul;18(1):203-9
references: 17549369
references: Int J Cancer. 2008 Oct 15;123(8):1941-9
references: 18661526
references: PLoS Genet. 2008 Jan;4(1):e236
references: 18208327
references: J Int Med Res. 2010 May-Jun;38(3):870-83
references: 20819423
references: Eur J Cancer. 2005 Sep;41(14):2176-83
references: 16182121
references: Ann Oncol. 2011 Feb;22(2):355-61
references: 20647221
references: Biochemistry. 1974 Feb 26;13(5):926-33
references: 4205029
references: Nat Rev Cancer. 2003 May;3(5):330-8
references: 12724731
references: Clin Cancer Res. 2006 Jul 1;12(13):3928-34
references: 16818689
references: Br J Cancer. 2001 Sep 14;85(6):827-30
references: 11556832
references: J Clin Oncol. 2001 Mar 15;19(6):1779-86
references: 11251009
references: J Clin Oncol. 1997 May;15(5):2030-9
references: 9164215
references: Int J Oncol. 2006 May;28(5):1303-10
references: 16596248
references: J Clin Oncol. 2006 Apr 1;24(10):1603-11
references: 16575011
references: Anticancer Res. 2004 Jul-Aug;24(4):2455-63
references: 15330198
references: Cancer Res. 2003 Sep 15;63(18):6004-7
references: 14522928
references: Br J Cancer. 2008 Sep 2;99(5):716-21
references: 18728661