title: Association between dietary folate intake and clinical outcome in head and neck squamous cell carcinoma.
abstract: BACKGROUND
  The association between dietary folate intake, two polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TYMS), and survival in head and neck squamous cell carcinoma (HNSCC) patients is not clarified.
  
  
  METHODS
  We conducted a retrospective cohort study of 437 HNSCC patients treated at Aichi Cancer Center. We evaluated the survival impact of pretreatment dietary folate intake, which was estimated using a food-frequency questionnaire, and two polymorphisms, MTHFR C677T and a 6-bp insertion/deletion in the 3'-untranslated region of TYMS, using multivariate proportional hazard models.
  
  
  RESULTS
  Patients with high folate intake (≥320 μg/day; n=144) had significantly higher survival than patients with low or medium folate intake (<320 μg/day; n=278; 79.1% versus 68.2%, respectively, P=0.020). This association was consistent with multivariate analyses adjusted for established prognostic factors (hazard ratio 0.56; 95% confidence interval 0.37-0.84). MTHFR and TYMS polymorphisms did not show significant association with survival, although the TYMS 6-bp insertion allele showed potential association with a reduced risk of death. Notably, no significant interaction was observed between folate intake and the two examined polymorphisms.
  
  
  CONCLUSIONS
  High pretreatment dietary folate intake was identified as an independent prognostic factor associated with improved clinical outcomes in HNSCC patients. Further study is warranted.
authors: Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya; Department of Otorhinolaryngology, Head and Neck Surgery, Nagoya City University Graduate School of Medical Sciences.
authors: D
authors: D
authors: Kawakita
authors: Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya; Department of Epidemiology, Nagoya University Graduate School of Medicine. Electronic address: kmatsuo@aichi-cc.jp.
authors: K
authors: K
authors: Matsuo
authors: Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya.
authors: F
authors: F
authors: Sato
authors: Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya.
authors: I
authors: I
authors: Oze
authors: Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya.
authors: S
authors: S
authors: Hosono
authors: Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya.
authors: H
authors: H
authors: Ito
authors: Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya.
authors: M
authors: M
authors: Watanabe
authors: Departments of Pathology and Molecular Diagnosis.
authors: Y
authors: Y
authors: Yatabe
authors: Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.
authors: N
authors: N
authors: Hanai
authors: Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.
authors: Y
authors: Y
authors: Hasegawa
authors: Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya.
authors: K
authors: K
authors: Tajima
authors: Department of Otorhinolaryngology, Head and Neck Surgery, Nagoya City University Graduate School of Medical Sciences.
authors: S
authors: S
authors: Murakami
authors: Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya; Department of Epidemiology, Nagoya University Graduate School of Medicine.
authors: H
authors: H
authors: Tanaka
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality; D015331:Cohort Studies; D004032:Diet; D005260:Female; D005492:Folic Acid; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000235:genetics*; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D011795:Surveys and Questionnaires; D013940:Thymidylate Synthase / Q000235:genetics*; D055815:Young Adult
chemical_list: D015778:Minor Histocompatibility Antigens; D005492:Folic Acid; C539735:MTHFD1 protein, human; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP); D013940:Thymidylate Synthase