title: Folate intake along with genetic polymorphisms in methylenetetrahydrofolate reductase and thymidylate synthase in patients with advanced gastric cancer.
abstract: BACKGROUND
  A relationship between dietary folate intake and efficacy of fluorouracil (FU) is supported by preclinical data. Furthermore, there are several reports that evaluated genetic polymorphisms of MTHFR (methylenetetrahydrofolate reductase) or TYMS (thymidylate synthase) and efficacy of FU. However, to our knowledge, there are no reports that evaluate simultaneously the effects of folate intake and genetic polymorphisms on clinical outcome of gastric cancer patients.
  
  
  METHODS
  We retrospectively analyzed the survival impact of estimated folate intake by a food frequency questionnaire and MTHFR and TYMS polymorphisms in 132 patients with advanced gastric cancer who were treated with first-line FU-based chemotherapy.
  
  
  RESULTS
  Median overall survival was 11.3 months (95% confidence interval, 9.4-13.4 mo) and median progression-free survival was 5.2 months (95% confidence interval, 4.1-6.3 mo). Patients with folate intake of >260 microg/day (n=88) showed longer overall survival compared with low folate intake (n=44; overall survival, 12.2 versus 8.4 mo). In a multivariate Cox model, patients who had folate intake of >260 microg/day, MTHFR 677 TT polymorphism, and TYMS-3' untranslated region 6-bp insertion were associated with better survival. Similar tendency was observed in progression-free survival. No interaction was observed between folate intake and favorable genotypes.
  
  
  CONCLUSIONS
  Folate intake and genetic polymorphisms of MTHFR and TYMS were associated with better clinical outcome by FU-based chemotherapy in advanced gastric cancer.
  
  
  CONCLUSIONS
  Our results suggested folate intake and folate-related genetic polymorphisms may play an important role in efficacy of FU-based chemotherapy in advanced gastric cancer.
authors.affiliation: Department of Clinical Oncology, Aichi Cancer Center Hospital, and Department of Epidemiology, Nagoya University Graduate School of Medicine, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Aichi, Japan. Kouheis0824@yahoo.co.jp
authors.forename: Kohei
authors.initials: K
authors.lastname: Shitara
authors.forename: Kei
authors.initials: K
authors.lastname: Muro
authors.forename: Seiji
authors.initials: S
authors.lastname: Ito
authors.forename: Akira
authors.initials: A
authors.lastname: Sawaki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tajika
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kawai
authors.forename: Tomoya
authors.initials: T
authors.lastname: Yokota
authors.forename: Daisuke
authors.initials: D
authors.lastname: Takahari
authors.forename: Takashi
authors.initials: T
authors.lastname: Shibata
authors.forename: Takashi
authors.initials: T
authors.lastname: Ura
authors.forename: Hidemi
authors.initials: H
authors.lastname: Ito
authors.forename: Satoyo
authors.initials: S
authors.lastname: Hosono
authors.forename: Takakazu
authors.initials: T
authors.lastname: Kawase
authors.forename: Miki
authors.initials: M
authors.lastname: Watanabe
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tajima
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yatabe
authors.forename: Hideo
authors.initials: H
authors.lastname: Tanaka
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D015996:Survival Rate; D013940:Thymidylate Synthase / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013940:Thymidylate Synthase