title: The effects of genomic polymorphisms in one-carbon metabolism pathways on survival of gastric cancer patients received fluorouracil-based adjuvant therapy.
abstract: 5-fluorouracil (5-FU) is widely used to treat patients with gastric cancer (GC). However, the response rate is quite heterogeneous. The single nucleotide polymorphisms (SNPs) and their interactions of genes in the one-carbon metabolism (OCM) pathway, including Methylenetetrahydrofolate reductase (MTHFR), Methionine synthase reductase (MTRR), Methionine synthase (MTR), and Thymidylate synthase (TS), significantly affect 5-FU metabolism. In this study, 650 stage II-III patients were recruited from 1998 to 2006. Among them, 251 received 5-FU treatment and other 399 patients were untreated. The Cox regression analysis, log-rank tests and Kaplan-Meier plots were adopted. In the chemotherapy cohort, MTRR 66 GA + GG genotypes decreased death risk, however, the protect effect of MTRR 66 GA + GG disappeared when GC patients simultaneously had MTHFR 677TT + TC or MTR 2756GG + GA genotypes. TS 5'-UTR 2R3R + 3R3R genotypes also prolonged overall survival of patients treated with 5-FU. And this favorable prognosis obviously enhanced when GC patients simultaneously had TS 3'-UTR DD + DI and TS 5'-UTR 2R3R + 3R3R genotypes. Our findings showed that the polymorphisms of MTRR 66 A > G and TS 5'-UTR 3R > 2R may be potential prognostic factors for GC patients receiving 5-FU.
authors.affiliation: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China.
authors.forename: Dongying
authors.initials: D
authors.lastname: Gu
authors.affiliation: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wu
authors.affiliation: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China.
authors.forename: Xinying
authors.initials: X
authors.lastname: Huo
authors.affiliation: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Surgery, Yixing People's Hospital, Yixing, 214200, China.
authors.forename: Yongfei
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Surgery, Yixing Cancer Hospital, Yixing, 214200, China.
authors.forename: Weida
authors.initials: W
authors.lastname: Gong
authors.affiliation: Department of Biomedical Sciences, City University of Hong Kong, Hong Kong.|CityU Shenzhen Research Institute, Shenzhen, 518000, China.
authors.forename: Ming-Liang
authors.initials: ML
authors.lastname: He
authors.affiliation: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Jinfei
authors.initials: J
authors.lastname: Chen
mesh_terms: D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D005838:Genotype; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D015996:Survival Rate
chemical_list: D009363:Neoplasm Proteins; D005472:Fluorouracil