Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of esophageal adenocarcinoma among cigarette smokers in the SBES cohort.

†<p>– Age modeled as a continuous variable,</p>‡<p>– WHR modeled as a continuous variable,</p>¶<p>– NSAID use modeled as a categorical variable (Current, Former, never).</p><p>T1: Tertile 1, T2: Tertile 2, T3: Tertile 3.</p>*<p>Test for trend was based on the likelihood-ratio test associated with addition of the variable under consideration in its continuous form.</p

Anthropometric measurements of all participants in the SBES cohort at baseline.

†<p>Two males had missing waist and hip circumferences at baseline.</p><p>Q1: Quartile 1, Q2: Quartile 2, Q3: Quartile 3, Q4: Quartile 4.</p><p>Waist-Hip ratio- Entire cohort: Q1 0.72-, Q2 0.91-, Q3 0.95-, Q4 0.99-; Males: Q1 0.72-, Q2 0.93-, Q3 0.96-, Q4 1.00-; Females: Q1 0.72-, Q2 0.81-, Q3 0.87-, Q4 0.91-.</p><p>Waist circumference – Entire chort: Q1 25.5-, Q2 37.1-, Q3 39.6-, Q4 42.5-; Males: Q1 25.5-, Q2 37.6-, Q3 39.8-, Q4 42.6-; Females: Q1 25.5-, Q2 33.5-, Q3 37.9-, Q4 40.8-.</p><p>Hip circumference - Entire chort: Q1 32.0-, Q2 39.5-, Q3 41.7-, Q4 43.9-; Males: Q1 32.0-, Q2 39.6-, Q3 41.7-, Q4 43.4-; Females: Q1 32.0-, Q2 39.0-, Q3 41.8-, Q4 40.8-.</p

Selected characteristics of all participants in the SBES cohort at baseline.

†<p>Current NSAID use history for one male participant was missing.</p

Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of esophageal adenocarcinoma (EA) for BMI and waist-hip ratio (WHR) in the SBES cohort.

†<p>– Age modeled as a continuous variable,</p>‡<p>– Cigarette smoking modeled as a categorical variable (Current, Former, Never),</p>¶<p>– NSAID use modeled as a categorical variable (Current, Former, Never).</p><p>Q1: Quartile 1, Q2: Quartile 2, Q3: Quartile 3, Q4: Quartile 4.</p>*<p>Test for trend was based on the likelihood-ratio test associated with addition of the variable under consideration in its continuous form.</p

Cohort characteristics.

<p>Cohort characteristics.</p

Examples of p16 mutations in Barrett's esophagus.

<p>A) C to T transition at basepair 247. B) 1 basepair deletion at nucleotide 289.</p

Mutations in p16/CDKN2a detected in esophagectomy patients.

<p>Headings are same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003809#pone-0003809-t002" target="_blank">Table 2</a>. Diagnosis is at the time of the esophagectomy.</p

High Goblet Cell Count Is Inversely Associated with Ploidy Abnormalities and Risk of Adenocarcinoma in Barrett’s Esophagus

<div><p>Purpose</p><p>Goblet cells may represent a potentially successful adaptive response to acid and bile by producing a thick mucous barrier that protects against cancer development in Barrett's esophagus (BE). The aim of this study was to determine the relationship between goblet cells (GC) and risk of progression to adenocarcinoma, and DNA content flow cytometric abnormalities, in BE patients.</p><p>Experimental Design</p><p>Baseline mucosal biopsies (N=2988) from 213 patients, 32 of whom developed cancer during the follow up period, enrolled in a prospective dynamic cohort of BE patients were scored in a blinded fashion, for the total number (#) of GC, mean # of GC/crypt (GC density), # of crypts with ≥ 1 GC, and the proportion of crypts with ≥1 GC, in both dysplastic and non-dysplastic epithelium separately. The relationship between these four GC parameters and DNA content flow cytometric abnormalities and adenocarcinoma outcome was compared, after adjustment for age, gender, and BE segment length.</p><p>Results</p><p>High GC parameters were inversely associated with DNA content flow cytometric abnormalities, such as aneuploidy, ploidy >2.7N, and an elevated 4N fraction > 6%, and with risk of adenocarcinoma. However, a Kaplan-Meier analysis showed that the total # of GC and the total # crypts with ≥1 GC were the only significant GC parameters (p<0.001 and 0.003, respectively).</p><p>Conclusions</p><p>The results of this study show, for the first time, an inverse relationship between high GC counts and flow cytometric abnormalities and risk of adenocarcinoma in BE. Further studies are needed to determine if GC depleted foci within esophageal columnar mucosa are more prone to neoplastic progression or whether loss of GC occurs secondary to underlying genetic abnormalities.</p></div

Results of univariate analysis regarding goblet cell parameters in patients who did or did not progress to cancer.

<p>NC = No cancer</p><p>C = Cancer</p><p>^ǂ p-value: test for the risk difference between absent/present of the feature</p><p>Results of univariate analysis regarding goblet cell parameters in patients who did or did not progress to cancer.</p

Members of the <i>Firmicutes</i> or <i>Bacteroidetes</i> phyla dominate the upper gastrointestinal tract microbiome.

<p>(A) Phylogenetic relationship of the top 45 OTUs recovered from each of the four sites sampled in individual participants. Respective phyla are noted above main branches of the phylogenetic tree. Numbers in parentheses represent total number of pyrosequencing reads recovered for a given species or genera across all samples followed by the fraction of participants in whom a relative abundance of ≥1.3% of a given species or genera were detected. (B) Species/genera-level profiles of top 45 OTUs detected by 454 sequencing in squamous esophagus, Barrett’s esophagus, stomach corpus and stomach antrum of indicated participants. Data arranged in order of increasing <i>Firmicutes</i> dominance. Individual species/genera are color-coded according to scheme presented in (A). Sequencing reads from brush samples were used when available, otherwise, data from biopsy samples are shown. Species reads were normalized to the total number of reads per corresponding site in a given individual. ^†Denotes samples collected at a second time point (P2 [t = 4 months]; P7 [t = 2 years]; P9 [t = 3 years]); <i>Hp+</i> indicates <i>H</i>. <i>pylori</i>-positive individual. Italicized participant IDs denote data from biopsy samples in cases where brush samples were not available for analysis.</p