title: Dietary folate and related micronutrients, folate-metabolising genes, and ovarian cancer survival.
abstract: OBJECTIVE
  Folate is essential for DNA synthesis and methylation and is implicated in tumour progression. Few studies have examined its role in ovarian cancer survival. Our objective was to determine relationships between intake of folate, related one-carbon nutrients, single nucleotide polymorphisms (SNPs) in folate-metabolising genes and survival following ovarian cancer diagnosis.
  
  
  METHODS
  This analysis included 1270 women with invasive epithelial ovarian cancer diagnosed in 2002-2006. Pre-diagnostic and some post-diagnostic lifestyle, dietary, and sociodemographic information was collected via self-administered questionnaires. DNA samples were genotyped for SNPs in methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR) and methionine synthase reductase (MTRR) genes. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression.
  
  
  RESULTS
  Multivariate analyses did not identify associations between higher pre-diagnostic intake of folate, folic acid, vitamins B2, B6, and B12, methionine, betaine or choline and survival overall. In stratified analyses, higher folic acid and folate intake was associated with significantly worse survival among women with mucinous tumours (HRs per 100 μg 1.30 and 1.43, respectively) and smokers (HRs per 100 μg 1.23 and 1.16 respectively). There was also a suggestion that higher supplemental folic acid use post-diagnosis was associated with worse survival (HR per 100 μg 1.03, 95%CI 1.00-1.05). MTHFR SNP rs2066470 was significantly associated with survival (per allele HR 0.81, 95%CI 0.67-0.98).
  
  
  CONCLUSIONS
  Our data provide little evidence that folate intake affects ovarian cancer survival. However, combined effects with smoking, and findings within the mucinous subtype and for post-diagnosis folic acid, warrant further investigation.
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Australia; School of Population Health, University of Queensland, Brisbane, Australia.
authors.forename: S C
authors.initials: SC
authors.lastname: Dixon
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors.forename: T I
authors.initials: TI
authors.lastname: Ibiebele
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Australia; School of Population Health, University of Queensland, Brisbane, Australia.
authors.forename: M M
authors.initials: MM
authors.lastname: Protani
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Beesley
authors.affiliation: Department of Gynaecological Oncology, Westmead Hospital, and Westmead Institute for Cancer Research, University of Sydney at the Westmead Millennium Institute, Westmead, Australia.
authors.forename: A
authors.initials: A
authors.lastname: deFazio
authors.affiliation: Brisbane Private Hospital, Brisbane, Australia.
authors.forename: A J
authors.initials: AJ
authors.lastname: Crandon
authors.affiliation: Royal North Shore Hospital, Sydney, Australia.
authors.forename: G B
authors.initials: GB
authors.lastname: Gard
authors.affiliation: Epworth Freemasons Hospital, Melbourne, Australia.
authors.forename: R M
authors.initials: RM
authors.lastname: Rome
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Australia; School of Population Health, University of Queensland, Brisbane, Australia.
authors.forename: P M
authors.initials: PM
authors.lastname: Webb
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Australia; School of Population Health, University of Queensland, Brisbane, Australia. Electronic address: Christina.Nagle@qimrberghofer.edu.au.
authors.forename: C M
authors.initials: CM
authors.lastname: Nagle
mesh_terms: D000368:Aged; D000428:Alcohol Drinking / Q000453:epidemiology; D001315:Australia / Q000453:epidemiology; D000077216:Carcinoma, Ovarian Epithelial; D016022:Case-Control Studies; D015331:Cohort Studies; D004032:Diet / Q000706:statistics & numerical data*; D005185:Fallopian Tube Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage* / Q000378:metabolism; D006801:Humans; D018977:Micronutrients / Q000008:administration & dosage*; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000453:epidemiology; D011795:Surveys and Questionnaires
chemical_list: D018977:Micronutrients; D005492:Folic Acid
keywords: Folate; One-carbon nutrients; Ovarian cancer survival; Single nucleotide polymorphisms