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Dietary flavonoid intake and Barrett's esophagus in western Washington State.

ABSTRACT: PURPOSE:Flavonoids, concentrated in fruits and vegetables, demonstrate in experimental studies chemopreventive properties in relation to Barrett's esophagus (BE), a precursor lesion for esophageal adenocarcinoma. One case-control investigation reported an inverse association between isoflavone intake and odds of BE, yet no epidemiologic study has considered other flavonoid classes, which are more commonly consumed by Americans. METHODS:We examined intake of total flavonoids, six flavonoid classes, and lignans among case-control study participants in western Washington State. Food frequency questionnaires were self-completed by BE cases with specialized intestinal metaplasia (n = 170) and matched controls (n = 183). RESULTS:In logistic regression models adjusted for age, sex, body mass index, and energy intake, the odds ratio (OR) for specialized intestinal metaplasia BE associated with anthocyanidin intake was 0.49 (95% confidence interval: 0.30-0.80, for quartiles 2-4 combined vs. quartile 1), for which wine and fruit juice were major dietary sources. More moderate decreased ORs were noted for flavanones, flavonols, isoflavones, and lignans. A modest increased OR was observed for flavones, for which pizza was the main dietary source in our population. CONCLUSIONS:Our findings of an inverse association between anthocyanidins and odds of BE suggest that adequate dietary intake of these compounds may lower risk of this cancer precursor lesion.

SUBMITTER: Petrick JL

PROVIDER: S-EPMC4567908 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Dietary flavonoid intake and Barrett's esophagus in western Washington State.

Petrick Jessica L JL Steck Susan E SE Bradshaw Patrick T PT Chow Wong-Ho WH Engel Lawrence S LS He Ka K Risch Harvey A HA Vaughan Thomas L TL Gammon Marilie D MD

Annals of epidemiology 20150605 10

<h4>Purpose</h4>Flavonoids, concentrated in fruits and vegetables, demonstrate in experimental studies chemopreventive properties in relation to Barrett's esophagus (BE), a precursor lesion for esophageal adenocarcinoma. One case-control investigation reported an inverse association between isoflavone intake and odds of BE, yet no epidemiologic study has considered other flavonoid classes, which are more commonly consumed by Americans.<h4>Methods</h4>We examined intake of total flavonoids, six f ...[more]

PMID: 26169148

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Project description:As the premalignant lesion of human esophageal adenocarcinoma (EAC), Barrett's esophagus (BE) is characterized by intestinal metaplasia in the normal esophagus (NE). Gene expression profiling with microarray and serial analysis of gene expression (SAGE) may help us understand the potential molecular mechanism of human BE.We analyzed three microarray datasets (two cDNA arrays and one oligonucleotide array) and one SAGE dataset with statistical tools, significance analysis of microarrays (SAM) and SAGE(Poisson), to identify individual genes differentially expressed in BE. Gene set enrichment analysis (GSEA) was used to identify a priori defined sets of genes that were differentially expressed. These gene sets were grouped according to either certain signaling pathways (GSEA curated), or the presence of consensus binding sequences of known transcription factors (GSEA motif). Immunohistochemical staining (IHC) was used to validate differential gene expression.Both SAM and SAGE(Poisson) identified 68 differentially expressed genes (55 BE genes and 13 NE genes) with an arbitrary cutoff ratio (> or =4-fold). With IHC on matched pairs of NE and BE tissues from 6 patients, these genes were grouped into 6 categories: category I (25 genes only expressed in BE), category II (5 genes only expressed in NE), category III (8 genes expressed more in BE than in NE), and category IV (2 genes expressed more in NE than in BE). Differential expression of the remaining genes was not confirmed by IHC either due to false discovery (category V), or lack of proper antibodies (category VI). Besides individual genes, the TGFbeta pathway and several transcription factors (CDX2, HNF1, and HNF4) were identified by GSEA as enriched pathways and motifs in BE. Apart from 9 target genes known to be up-regulated in BE, IHC staining confirmed up-regulation of 19 additional CDX1 and CDX2 target genes in BE.Our data suggested an important role of CDX1 and CDX2 in the development of BE. The IHC-confirmed gene list will lead to future studies on the molecular mechanism of BE.

Dataset Information

Dietary flavonoid intake and Barrett's esophagus in western Washington State.

Publications

Dietary flavonoid intake and Barrett's esophagus in western Washington State.

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