title: Intakes of dietary folate and other B vitamins are associated with risks of esophageal adenocarcinoma, Barrett's esophagus, and reflux esophagitis.
abstract: Folate is implicated in carcinogenesis via effects on DNA synthesis, repair, and methylation. Efficient folate metabolism requires other B vitamins and is adversely affected by smoking and alcohol. Esophageal adenocarcinoma (EAC) may develop through a process involving inflammation [reflux esophagitis (RE)] leading to metaplasia [Barrett's esophagus (BE)] and carcinoma. Within a population-based, case-control study, we investigated associations between dietary folate and related factors and risks of EAC, BE, and RE. EAC and BE cases had histologically confirmed disease; RE cases had endoscopically visible inflammation. Controls, age-sex frequency matched to EAC cases, were selected through population and general practice registers. Participants underwent structured interviews and completed food-frequency questionnaires. Multivariate ORs and 95% CIs were computed using logistic regression. A total of 256 controls and 223 EAC, 220 BE, and 219 RE cases participated. EAC risk decreased with increasing folate intake (OR highest vs. lowest = 0.56; 95% CI: 0.31, 1.00; P-trend < 0.01). Similar trends were found for BE (P-trend < 0.01) and RE (P-trend = 0.01). Vitamin B-6 intake was significantly inversely related to risks of all 3 lesions. Riboflavin intake was inversely associated with RE. Vitamin B-12 intake was positively associated with EAC. For EAC, there was a borderline significant interaction between folate intake and smoking (P-interaction = 0.053); compared with nonsmokers with high (≥ median) folate intake, current smokers with low intakes (<median) had an 8-fold increased risk (OR: 8.15; 95% CI: 3.61, 18.40). The same group had increased BE risk (OR: 2.93; 95% CI: 1.24, 6.92; P-interaction = 0.12). Folate and other dietary methyl-group factors are implicated in the etiology of EAC and its precursors.
authors.affiliation: National Cancer Registry Ireland, Cork, Ireland.
authors.forename: Linda
authors.initials: L
authors.lastname: Sharp
authors.forename: Anne-Elie
authors.initials: AE
authors.lastname: Carsin
authors.forename: Marie M
authors.initials: MM
authors.lastname: Cantwell
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Anderson
authors.forename: Liam J
authors.initials: LJ
authors.lastname: Murray
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology*; D000368:Aged; D001471:Barrett Esophagus / Q000453:epidemiology*; D016022:Case-Control Studies; D004032:Diet; D004938:Esophageal Neoplasms / Q000453:epidemiology*; D004942:Esophagitis, Peptic / Q000453:epidemiology*; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D014803:Vitamin B Complex / Q000008:administration & dosage*
chemical_list: D014803:Vitamin B Complex; D005492:Folic Acid