Intakes of Dietary Folate and Other B Vitamins Are Associated with Risks of Esophageal Adenocarcinoma, Barrett's Esophagus, and Reflux Esophagitis

Linda Sharp*, Anne-Elie Carsin, Marie M. Cantwell, Lesley A. Anderson, Liam J. Murray, FINBAR Study Group

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

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 [Barretts 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.

Original languageEnglish
Pages (from-to)1966-1973
Number of pages8
JournalJournal of Nutrition
Volume143
Issue number12
Early online date16 Oct 2013
DOIs
Publication statusPublished - 1 Dec 2013

Bibliographical note

Acknowledgments

The authors thank Siobhan Reynolds, Majella Gallagher, Carol Anderson, and Martin McAnaespie for subject recruitment, Damian McManus for help with classifying the tumor sites, and Helen Mulholland for helpful comments on an earlier draft of the manuscript. The FINBAR study group members are L.J. Murray, L.A. Anderson (Queen's University Belfast); B.T. Johnston, R.G.P. Watson, J. McGuigan, H.R. Ferguson (Belfast Health and Social Care Trust, Belfast, Country Antrim, UK); S.J. Murphy (St Vincent's Hospital, Dublin, Ireland); J.V. Reynolds (St James' Hospital, Dublin, Ireland); and H. Comber (National Cancer Registry Ireland). L.J.M. and L.A.A. designed the FINBAR study; L.A.A. conducted the study; L.J.M. supervised the study; M.M.C. provided dietary assessment expertise; L.S. had the idea for this analysis; A.-E.C. and L.S. analyzed data; and L.S. wrote the paper and has primary responsibility for final content. All authors read and approved the final manuscript.

Supported by a Ireland-Northern Ireland Co-operation Research Project Grant sponsored by the Research and Development Office, Belfast and the Health Research Board Dublin, and by the Ulster Cancer Foundation, Northern Ireland. The reflux esophagitis data collection was supported by a Research and Development Office Clinical Fellowship.

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