title: High intake of folate from food sources is associated with reduced risk of esophageal cancer in an Australian population.
abstract: Folate plays a key role in DNA synthesis and methylation. Limited evidence suggests high intake may reduce risks of esophageal cancer overall; however, associations with esophageal cancer subtypes and Barrett's esophagus (BE), a precancerous lesion, remain unexplored. We evaluated the relation between intake of folate, B vitamins, and methyl-group donors (methionine, choline, betaine) from foods and supplements, polymorphisms in key folate-metabolizing genes, and risk of BE, esophageal adenocarcinoma (EAC), and esophageal squamous cell carcinoma (ESCC) in 2 population-based case-control studies in Australia. BE patients without (n = 266) or with (n = 101) dysplasia were compared with population controls (n = 577); similarly, EAC (n = 636) or ESCC (n = 245) patients were compared with population controls (n = 1507) using multivariable adjusted logistic regression. Increasing intake of folate from foods was associated with reduced EAC risk (P-trend = 0.01) and mitigated the increased risks of ESCC associated with smoking and alcohol consumption. In contrast, high intake of folic acid from supplements was associated with a significantly elevated risk of BE with dysplasia. High intakes of riboflavin and methionine from food were associated with increased EAC risk, whereas increasing betaine intake was associated with reduced risks of BE without (P-trend = 0.004) or with dysplasia (P-trend = 0.02). Supplemental thiamin, riboflavin, niacin, and vitamin B-12 were associated with increased EAC risk. There were no consistent associations between genetic polymorphisms studied and BE or EAC risk. High intake of folate-containing foods may reduce risk of EAC, but our data raise the possibility that folic acid supplementation may increase risks of BE with dysplasia and EAC.
authors.affiliation: Queensland Institute of Medical Research, Genetics and Population Health Division, Herston, Brisbane, Australia. Torukiri.Ibiebele@qimr.edu.au
authors.forename: Torukiri I
authors.initials: TI
authors.lastname: Ibiebele
authors.forename: Maria Celia
authors.initials: MC
authors.lastname: Hughes
authors.forename: Nirmala
authors.initials: N
authors.lastname: Pandeya
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhao
authors.forename: Grant
authors.initials: G
authors.lastname: Montgomery
authors.forename: Nick
authors.initials: N
authors.lastname: Hayward
authors.forename: Adèle C
authors.initials: AC
authors.lastname: Green
authors.forename: David C
authors.initials: DC
authors.lastname: Whiteman
authors.forename: Penelope M
authors.initials: PM
authors.lastname: Webb
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000517:prevention & control*; D000328:Adult; D000368:Aged; D000428:Alcohol Drinking; D001315:Australia / Q000453:epidemiology; D001471:Barrett Esophagus / Q000453:epidemiology / Q000473:pathology / Q000517:prevention & control*; D001622:Betaine / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000517:prevention & control; D016022:Case-Control Studies; D004032:Diet; D019587:Dietary Supplements / Q000009:adverse effects; D004938:Esophageal Neoplasms / Q000453:epidemiology / Q000517:prevention & control*; D004947:Esophagus / Q000473:pathology; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008715:Methionine / Q000009:adverse effects; D008875:Middle Aged; D012307:Risk Factors; D012907:Smoking; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D014803:Vitamin B Complex; D001622:Betaine; D005492:Folic Acid; D008715:Methionine