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

<i>Streptococcus</i> to <i>Prevotella</i> species ratio corresponds to phylogenetic distance sample clustering and correlates with Barrett’s esophagus risk factors.

<p>(A) Cluster analysis of KR distances between microbial communities of individual study samples. Pyroseq. <i>Strep</i>:<i>Prev</i> ratio was calculated using relative abundance of mapped reads for all <i>Streptococcus</i> and <i>Prevotella</i> species as determined by pyrosequencing. ddPCR <i>Strep</i>:<i>Prev</i> ratio was calculated using copies/μl of a <i>Streptococcus</i> or <i>Prevotella</i>-specific 16s rRNA gene segment as determined by droplet digital PCR. Samples color-coded based on the majority of calculated Pyroseq. <i>Strep</i>:<i>Prev</i> ratios in a group being <0.5 (blue), 0.5–1.5 (green), 1.5–4.0 (magenta) or >4.0 (red). (B) Boxplots comparing <i>Streptococcus</i> to <i>Prevotella</i> ratio as determined by pyrosequencing and ddPCR. The central line within each box represents the median of the data, the whiskers represent the 5^th and 95^th percentiles and data outside that range are plotted as individual points. (C) Relationship of <i>Streptococcus</i> to <i>Prevotella</i> ratio (measured by ddPCR) and waist-hip ratio of all male participants segregated by anatomic site. Strength of association between these two variables was determined by Pearson’s correlation test with correlation coefficient squared (r²) values as indicated. (D) Relationship of <i>Streptococcus</i> to <i>Prevotella</i> ratios (measured by ddPCR) and hiatal hernia length in all participants segregated by anatomic site. Strength of association tween these two variables was determined by Pearson’s correlation test with correlation coefficient squared (r²) values as indicated.</p