Risk Of Barrett's Esophagus Research Articles

Abstract 6184: A novel approach to Barrett's esophagus risk stratification: Whole-slide image analysis for aneuploidy detection

Abstract Background Barrett’s esophagus (BE) is the only known precursor of esophageal adenocarcinoma (EAC) and there is a need for biomarkers in BE for risk stratification for cancer progression. Aneuploidy has been suggested as a factor in the development, initiation or progression of EAC in patients with BE, and it has been found predictive for EAC progression (Hadjinicolaou, et al. 2020, Sikkema, et al. 2009). However, current assays for detecting aneuploidy require valuable tissue, hence validation studies are limited. We hypothesise that routine histology images can be used to detect ploidy status. We aim to develop a sensitive, accurate, and easy-to-use deep learning tool for this purpose. Methods We used a weakly supervised deep learning-based approach called clustering-constrained-attention multiple-instance learning (CLAM) (Lu et al., 2021) to detect aneuploidy on hematoxylin and eosin-stained whole slide images of endoscopical biopsies from BE, for which the ploidy status had been determined by flow cytometry. To benchmark the model’s performance, we also trained a traditional fully supervised algorithm, ResNet50 (He et al., 2016), with the same dataset. The models were trained on 388 slides (51 aneuploid) from the Seattle Barrett’s Esophagus Annotated Resource (BEAR) and then applied to an independent test cohort of BEAR patients, consisting of 279 slides (36 aneuploid). Results The multi-attention-branch CLAM model achieved AUC of 0.82 and 76.4% balanced accuracy for aneuploidy on the internal test subset (10% of the cohort). On the independent test dataset, the model achieved AUC of 0.85 and 79.3% balanced accuracy, while performance of the fully supervised model was AUC of 0.65 and 33.1 balanced accuracy. In a challenging subset for image-based diagnosis, including 253 samples (29 aneuploid) without dysplasia or atypical mitosis (a major feature of aneuploidy samples) the model achieved a 67.6% accuracy and an AUC of 0.83. Both the flow results (p=2.84e-7) and the model's predictions (p=2.18e-3) revealed a correlation between progression to EAC and ploidy status. Conclusion We developed a deep learning model for predicting aneuploidy in BE biopsies. The weakly-supervised approach can perform much better compared to the traditional fully-supervised model. Aneuploidy is correlated with cancer progression and stands as a promising candidate for the prediction of cancer progression in BE patients. Although atypical mitosis is the primary histological indicator of aneuploidy, our model can still make aneuploid predictions in the absence of atypical mitosis, as it doesn't rely solely on a single parameter. Our model is efficient, capable of processing hundreds of samples resource-effectively, and thus an ideal adjunct to standard histologic evaluation. This classifier may facilitate molecular-based improvements in identifying individuals at high risk of progression. Citation Format: Caner Ercan, Xiaoxi Pan, Thomas G. Paulson, Matthew D. Stachler, Carlo C. Maley, Yinyin Yuan. A novel approach to Barrett's esophagus risk stratification: Whole-slide image analysis for aneuploidy detection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6184.

Causal relationships between dietary habits and Barrett's esophagus risk: a univariable and multivariable Mendelian randomization study.

Aims: Dietary habits are reported to be associated with Barrett's esophagus (BE) risk; however, whether there is a causal relationship remains controversial. Here, we systematically examined the causal effects of genetically predicted dietary habits on BE risk through a Mendelian randomization (MR) analysis approach. Methods: Data for exposures were obtained from the UK Biobank (UKB), while the summary-level data for outcomes were obtained from a large sample-size GWAS meta-analysis. Genetic variants associated with 17 ordinary dietary habits at the genome-wide significance level were regarded as instrumental variables (IVs). Univariable and multivariable MR analyses were conducted to explore the causal relationships between dietary habits and BE risk. Sensitivity analyses were implemented to evaluate robustness of the results and determine the potential pleiotropy bias. Results: Univariable MR (UVMR) analysis showed that genetic predisposition to alcohol intake frequency, cooked vegetable intake, beef intake, bread intake, fresh fruit intake, salad/raw vegetable intake, and dried fruit intake were associated with BE risk, with all P values <0.05. After adjusting confounders, the effects of four dietary habits on BE risk persisted; multivariable MR (MVMR) analysis revealed that alcohol intake frequency (adjusted odds ratio (OR) = 1.74 (1.34, 2.27); P = 3.42 × 10-5) was causally associated with higher BE risk, the cooked vegetable intake (adjusted OR = 2.64 (1.16, 5.97); P = 0.02) had suggestively increased BE risk, while higher consumption of bread (adjusted OR = 0.54 (0.32-0.91); P = 0.02) and fresh fruit (adjusted OR = 0.34 (0.15, 0.77); P = 0.01) were suggestively associated with lower BE risk. Conclusions: These MR analyses demonstrate evidence of causal relationships between dietary habits and BE risk. These findings provide new insights into targeted dietary intervention strategies for BE prevention.

Mechanisms for the Sex-Specific Effect of H. Pylori on Risk of Gastroesophageal Reflux Disease and Barrett's Esophagus.

Mechanisms for how Helicobacter pylori infection affects risk of gastroesophageal reflux disease (GERD) and Barrett's esophagus are incompletely understood and might differ by sex. In a case-control study nested in the Melbourne Collaborative Cohort Study with 425 GERD cases and 169 Barrett's esophagus cases (identified at 2007-2010 follow-up), we estimated sex-specific odds ratios for participants who were H. pylori seronegative versus seropositive at baseline (1990-1994). To explore possible mechanisms, we (i) compared patterns of H. pylori-induced gastritis by sex using serum pepsinogen-I and gastrin-17 data and (ii) quantified the effect of H. pylori seronegativity on Barrett's esophagus mediated by GERD using causal mediation analysis. For men, H. pylori seronegativity was associated with 1.69-fold [95% confidence interval (CI), 1.03-2.75] and 2.28-fold (95% CI, 1.27-4.12) higher odds of GERD and Barrett's esophagus, respectively. No association was observed for women. H. pylori-induced atrophic antral gastritis was more common in men (68%) than in women (56%; P = 0.015). For men, 5 of the 15 per 1,000 excess Barrett's esophagus risk from being seronegative were mediated by GERD. Men, but not women, who were H. pylori seronegative had increased risks of GERD and Barrett's esophagus. A possible explanation might be sex differences in patterns of H. pylori-induced atrophic antral gastritis, which could lead to less erosive reflux for men. Evidence of GERD mediating the effect of H. pylori on Barrett's esophagus risk among men supports this proposed mechanism. The findings highlight the importance of investigating sex differences in the effect of H. pylori on risk of GERD and Barrett's esophagus in future studies.

Systematic review with meta-analysis: the effects of family history on the risk of Barrett's oesophagus and oesophageal adenocarcinoma.

SummaryBackgroundCurrent guidelines recommend different screening approaches for individuals with a family history of Barrett's oesophagus (BO) or oesophageal adenocarcinoma (OAC), varying from no screening to screening all individuals with a positive family history.AimsTo determine evidence‐based risk estimates for individuals with a family history of BO or OACMethodsWe systematically searched Pubmed, Embase and Cochrane Library until October 2020 to identify all studies that reported on the association between family history and the risk of BO and OAC. Pooled summary estimates of adjusted relative risks and prevalence of familial BO/OAC with 95% confidence intervals (CIs) were calculated using a random effects model.ResultsFourteen studies comprising 16 189 BO/OAC patients were analysed. Familial clustering was seen in 8.84% (95% CI: 5.54‐13.82) and 4.37% (95% CI: 2.15‐8.69) of patients with BO and OAC, respectively (nine studies). Screening first‐degree relatives of BO patients had a diagnostic yield between 12% and 44% for BO (four studies). However, the yield for high‐grade dysplasia and OAC was low (<2%). Individuals with a positive family history had a higher risk of having BO (aRR 3.26; 95% CI 1.43‐7.40; I 2 = 46%; three studies) and OAC (aRR 2.19; 95% CI 1.14‐4.21; I 2 = 48%; five studies) compared to individuals without a family history.ConclusionsA verified family history of BO or OAC is a strong risk factor for both BO and OAC. A positive family history could be a clinically meaningful way to identify high‐risk individuals who may benefit from early detection strategies.

Correlation Between Traditional Barrett's Esophagus Risk Factors and Gastroesophageal Acid Reflux and Esophageal Mucosal Injury

Introduction: Repeated mucosal injury from gastroesophageal reflux (GER) causes Barrett’s esophagus (BE). We studied correlation between traditional BE risk factors and the degree of gastroesophageal acid reflux and mucosal injury. Methods: Consecutive adults who underwent pH-impedance monitoring off therapy between Oct 2013-March 2020 were included. Patients with major motility disorders were excluded. Acid exposure time (AET) was used to determine the degree of gastroesophageal acid reflux. Mucosal injury was assessed using distal mean nocturnal basal impedance (dMNBI) which measures increased mucosal permeability from reflux injury. The correlations were assessed on univariable and multivariable linear regression models. Results: After excluding 33 for major motility disorder, 219 patients were included. On multivariate model, older age (p=0.038), White race (p=0.005), and higher BMI (p=0.015) had positive correlation with AET, while sex (p=0.154) and smoking (p=0.193) were not. Non-white patients averaged 50% (95%CI, 20-70%) lower AET, AET increased with age up to 60 years and with BMI up to 33 kg/m 2 . Inverse correlation observed between dMNBI and all the risk factors and AET. On multivariate analysis, only AET (p<.001) had significant correlation with dMNBI, male sex had borderline correlation (p=0.052) and none with age (p=0.140), race (p=0.117), smoking status (p=0.461), and BMI (p=0.109). Conclusion: Differential mucosal injury from GER noted between different BE risk factors; age, obesity, and White race increase degree of acid reflux, while male sex likely has higher degree of injury from acid reflux. These observations are insightful in developing a strategy to mitigate BE risk. Funding Statement: None. Declaration of Interests: None. Ethics Approval Statement: This study was approved by the Creighton University Institutional Review Board.

Effect of nonsteroidal anti-inflammatory drugs on Barrett's esophagus risk: a systematic review and meta-analysis

ObjectiveConflicting evidence exists regarding the effect of NSAIDs on the risk of Barrett’s esophagus. The purpose of this study is to systematically assess this effect through a meta-analysis. MethodsAccordingly, clinical studies on NSAID use and Barrett’s esophagus risk were searched on PubMed, Embase, and the Cochrane Library. Following this, meta-analyses were conducted using the RevMan 5.3 software. The pooled odds ratio (OR) and corresponding 95% confidence interval (CI) were used as the effect size. ResultsSeven eligible studies (one cohort study and six case-control studies) were included for the present meta-analysis by adopting a fixed-effect model, which demonstrated that NSAIDs could reduce Barrett’s esophagus risk (OR: 0.84, 95%CI:0.75−0.94, P＜0.05). Moreover, subgroup analyses done according to sex showed that NSAIDs could reduce Barrett’s esophagus risk in females (OR 0.85; 95% CI 0.73–0.99; P = 0.04), without heterogeneity between studies (P = 1.00 and I2 = 0%). However, this relationship was not evident in males (OR 0.85; 95% CI 0.68–1.07; P = 0.16). ConclusionsOverall, this meta-analysis provided high quality evidence that use of NSAIDs is associated with a reduced risk of Barrett’s esophagus. However, the presence of a sex-dependent difference remains to be clarified.

Dietary fruit, vegetable, fat, and red and processed meat intakes and Barrett's esophagus risk: a systematic review and meta-analysis.

The relationships between dietary fruit, vegetable, fat, and red and processed meat intakes and Barrett’s esophagus (BE) risk remain inconclusive. We conducted a systematic review and meta-analysis to summarize the available evidence on these issues. PubMed, EMBASE and the Cochrane Library were searched for studies published from inception through October 2015. A total of eight studies were included in this analysis. Fruit intake was not associated with BE risk (OR = 0.65, 95% CI = 0.37–1.13), but vegetable intake was strongly associated with BE risk (OR = 0.45, 95% CI = 0.29–0.71). Saturated fat, red meat and processed meat intakes were not associated with BE risk with OR = 1.25 (95% CI = 0.82–1.91), OR = 0.85 (95% CI = 0.61–1.17) and OR = 1.03 (95% CI = 0.73–1.46), respectively. Dietary vegetable not fruits intake may be associated with decreased BE risk. Fat and red and processed meat intakes may not contribute to an increased BE risk. Well-designed, large prospective studies with better established dose-response relationships are needed to further validate these issues.

Inverse Association Between Gluteofemoral Obesity and Risk ofBarrett's Esophagus in a Pooled Analysis.

Gluteofemoral obesity (determined by measurement of subcutaneous fat in the hip and thigh regions) could reduce risks of cardiovascular and diabetic disorders associated with abdominal obesity. We evaluated whether gluteofemoral obesity also reduces the risk of Barrett's esophagus (BE), a premalignant lesion associated with abdominal obesity. We collected data from non-Hispanic white participants in 8 studies in the Barrett's and Esophageal Adenocarcinoma Consortium. We compared measures of hip circumference (as a proxy for gluteofemoral obesity) from cases of BE (n= 1559) separately with 2 control groups: 2557 population-based controls and 2064 individuals with gastroesophageal reflux disease (GERD controls). Study-specific odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using individual participant data and multivariable logistic regression and combined using a random-effects meta-analysis. We found an inverse relationship between hip circumference and BE (OR per 5-cm increase, 0.88; 95% CI, 0.81-0.96), compared with population-based controls in a multivariable model that included waist circumference. This association was not observed in models that did not include waist circumference. Similar results were observed in analyses stratified by frequency of GERD symptoms. The inverse association with hip circumference was statistically significant only among men (vs population-based controls: OR, 0.85; 95% CI, 0.76-0.96 for men; OR, 0.93; 95% CI, 0.74-1.16 for women). For men, within each category of waist circumference, a larger hip circumference was associated with a decreased risk of BE. Increasing waist circumference was associated with an increased risk of BE in the mutually adjusted population-based and GERD control models. Although abdominal obesity is associated with an increased risk of BE, there is an inverse association between gluteofemoral obesity and BE, particularly among men.

Predicting Barrett's Esophagus in Families: An Esophagus Translational Research Network (BETRNet) Model Fitting Clinical Data to a Familial Paradigm.

Barrett's esophagus is often asymptomatic and only a small portion of Barrett's esophagus patients are currently diagnosed and under surveillance. Therefore, it is important to develop risk prediction models to identify high-risk individuals with Barrett's esophagus. Familial aggregation of Barrett's esophagus and esophageal adenocarcinoma, and the increased risk of esophageal adenocarcinoma for individuals with a family history, raise the necessity of including genetic factors in the prediction model. Methods to determine risk prediction models using both risk covariates and ascertained family data are not well developed. We developed a Barrett's Esophagus Translational Research Network (BETRNet) risk prediction model from 787 singly ascertained Barrett's esophagus pedigrees and 92 multiplex Barrett's esophagus pedigrees, fitting a multivariate logistic model that incorporates family history and clinical risk factors. The eight risk factors, age, sex, education level, parental status, smoking, heartburn frequency, regurgitation frequency, and use of acid suppressant, were included in the model. The prediction accuracy was evaluated on the training dataset and an independent validation dataset of 643 multiplex Barrett's esophagus pedigrees. Our results indicate family information helps to predict Barrett's esophagus risk, and predicting in families improves both prediction calibration and discrimination accuracy. Our model can predict Barrett's esophagus risk for anyone with family members known to have, or not have, had Barrett's esophagus. It can predict risk for unrelated individuals without knowing any relatives' information. Our prediction model will shed light on effectively identifying high-risk individuals for Barrett's esophagus screening and surveillance, consequently allowing intervention at an early stage, and reducing mortality from esophageal adenocarcinoma. Cancer Epidemiol Biomarkers Prev; 25(5); 727-35. ©2016 AACR.

A newly identified susceptibility locus near FOXP1 modifies the association of gastroesophageal reflux with Barrett's esophagus.

Important risk factors for esophageal adenocarcinoma and its precursor, Barrett's esophagus, include gastroesophageal reflux disease, obesity, and cigarette smoking. Recently, genome-wide association studies have identified seven germline single-nucleotide polymorphisms (SNP) that are associated with risk of Barrett's esophagus and esophageal adenocarcinoma. Whether these genetic susceptibility loci modify previously identified exposure-disease associations is unclear. We analyzed exposure and genotype data from the BEACON Consortium discovery phase GWAS, which included 1,516 esophageal adenocarcinoma case patients, 2,416 Barrett's esophagus case patients, and 2,187 control participants. We examined the seven newly identified susceptibility SNPs for interactions with body mass index, smoking status, and report of weekly heartburn or reflux. Logistic regression models were used to estimate ORs for these risk factors stratified by SNP genotype, separately for Barrett's esophagus and esophageal adenocarcinoma. The odds ratio for Barrett's esophagus associated with at least weekly heartburn or reflux varied significantly with the presence of at least one minor allele of rs2687201 (nominal P = 0.0005, FDR = 0.042). ORs (95% CIs) for weekly heartburn or reflux among participants with 0, 1, or 2 minor alleles of rs2687201 were 6.17 (4.91-7.56), 3.56 (2.85-4.44), and 3.97 (2.47-6.37), respectively. No statistically significant interactions were observed for smoking status and body mass index. Reflux symptoms are more strongly associated with Barrett's esophagus risk among persons homozygous for the major allele of rs2687201, which lies approximately 75 kb downstream of the transcription factor gene FOXP1. The novel gene-exposure interaction discovered in this study provides new insights into the etiology of esophageal adenocarcinoma.

Polymorphisms in Genes of Relevance for Oestrogen and Oxytocin Pathways and Risk of Barrett's Oesophagus and Oesophageal Adenocarcinoma: A Pooled Analysis from the BEACON Consortium.

BackgroundThe strong male predominance in oesophageal adenocarcinoma (OAC) and Barrett’s oesophagus (BO) continues to puzzle. Hormonal influence, e.g. oestrogen or oxytocin, might contribute.MethodsThis genetic-epidemiological study pooled 14 studies from three continents, Australia, Europe, and North America. Polymorphisms in 3 key genes coding for the oestrogen pathway (receptor alpha (ESR1), receptor beta (ESR2), and aromatase (CYP19A1)), and 3 key genes of the oxytocin pathway (the oxytocin receptor (OXTR), oxytocin protein (OXT), and cyclic ADP ribose hydrolase glycoprotein (CD38)), were analysed using a gene-based approach, versatile gene-based test association study (VEGAS).ResultsAmong 1508 OAC patients, 2383 BO patients, and 2170 controls, genetic variants within ESR1 were associated with BO in males (p = 0.0058) and an increased risk of OAC and BO combined in males (p = 0.0023). Genetic variants within OXTR were associated with an increased risk of BO in both sexes combined (p = 0.0035) and in males (p = 0.0012). We followed up these suggestive findings in a further smaller data set, but found no replication. There were no significant associations between the other 4 genes studied and risk of OAC, BO, separately on in combination, in males and females combined or in males only.ConclusionGenetic variants in the oestrogen receptor alpha and the oxytocin receptor may be associated with an increased risk of BO or OAC, but replication in other large samples are needed.

Metabolic Syndrome Increases Risk of Barrett Esophagus in the Absence of Gastroesophageal Reflux

To evaluate the association between metabolic syndrome (MetS) and risk of Barrett esophagus (BE) using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database compared with 2 control groups--Medicare population controls and endoscopy controls. BE principally arises as an adaptation to the proinflammatory state induced by gastroesophageal reflux disease (GERD). The relationship between obesity and BE is presumed to be mediated by GERD. However, evidence suggests central adiposity also increases risk of BE independent of GERD. Central adiposity is one risk factor defining MetS, which confers a systemic proinflammatory state--a potential GERD-independent mechanism by which obesity could increase the risk of BE. MetS was defined as diagnosis of at least 3 of the following conditions: obesity, elevated triglycerides, high blood pressure, and elevated fasting glucose. Multivariable logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals. In 2198 incident BE cases, prior MetS was significantly associated with BE (odds ratio, 1.20; 95% confidence interval: 1.07, 1.36) compared with population controls. However, GERD status modified the association; among those without prior GERD, MetS increased risk of BE by 34%; however, no association was observed among those with a prior GERD diagnosis (P-value for effect modification <0.001). MetS was not associated with risk of BE compared with endoscopy controls. MetS increased the risk of BE compared with population controls, an association driven by and confined to the non-GERD stratum. MetS may mediate an association between central adiposity and BE for those without GERD.

Metabolic syndrome and the risk of Barrett's oesophagus in white males.

Few studies have examined the association between metabolic syndrome and Barrett's oesophagus (BO). Whether metabolic syndrome confers a risk greater than the sum of its components is unknown. To investigate associations between metabolic syndrome, its components and BO in white males. We conducted a case-control study among eligible symptomatic patients scheduled for elective oesophagogastroduodenoscopy and a sample of patients eligible for screening colonoscopy recruited at primary care clinics. Metabolic syndrome was defined as the presence of at least three of: high waist-to-hip ratio (WHR), hypertriglyceridaemia, low high-density lipoprotein cholesterol, hypertension or diabetes. We used multivariate logistic regression to calculate odds ratios (OR) and 95% confidence intervals (95% CI). There were 244 BO cases, 209 colonoscopy and 615 endoscopy controls. Comparing BO cases with all controls, metabolic syndrome was significantly associated with BO (OR=1.59, 95% CI 1.05-2.40) and there was a dose effect with increasing number of metabolic syndrome components (Ptrend <0.001); when all five components were present, the OR was 2.61 (95% CI 1.14-5.99). We found that among the components, high WHR, hypertension and hypertriglyceridaemia were associated with increased risk of BO. When we compared cases with the control groups separately, metabolic syndrome was associated with BO for comparisons with endoscopy controls (OR=1.67, 95% CI 1.10-2.55) but not colonoscopy controls (OR=0.87, 95% CI 0.49-1.54). Associations with individual components also depended on the comparison group. Metabolic syndrome is associated with an increased risk of Barrett's oesophagus in men undergoing endoscopy. Metabolic syndrome may confer additional risk of Barrett's oesophagus separate from obesity.

Vitamin D Receptor Polymorphisms Are Associated with Reduced Esophageal Vitamin D Receptor Expression and Reduced Esophageal Adenocarcinoma Risk.

Epidemiological studies indicate that vitamin D exerts a protective effect on the development of various solid cancers. However, concerns have been raised regarding the potential deleterious role of high vitamin D levels in the development of esophageal adenocarcinoma (EAC). This study investigated genetic variation in the vitamin D receptor (VDR) in relation to its expression and risk of Barrett esophagus (BE) and EAC. VDR gene regulation was investigated by immunohistochemistry, reverse transcriptase-polymerase chain reaction (RT-PCR) and gel shift assays. Fifteen haplotype tagging single-nucleotide polymorphisms (SNPs) of the VDR gene were analyzed in 858 patients with reflux esophagitis (RE), BE or EAC and 202 healthy controls. VDR mRNA expression was higher in BE compared with squamous epithelium. VDR protein was located in the nucleus in BE. An rs1989969T/rs2238135G haplotype was identified in the 5' regulatory region of the VDR gene. It was associated with an approximately two-fold reduced risk of RE, BE and EAC. Analysis of a replication cohort was done for BE that confirmed this. The rs1989969T allele causes a GATA-1 transcription factor binding site to appear. The signaling of GATA-1, which is regarded as a negative transcriptional regulator, could explain the findings for rs1989969. The rs2238135G allele was associated with a significantly reduced VDR expression in BE; for the rs1989969T allele, a trend in reduced VDR expression was observed. We identified a VDR haplotype associated with reduced esophageal VDR expression and a reduced incidence of RE, BE and EAC. This VDR haplotype could be useful in identifying individuals who benefit most from vitamin D chemoprevention.

Total body fat and the risk of Barrett's oesophagus – A bioelectrical impedance study

BackgroundBody mass index is associated with the risk of Barrett's oesophagus (BO). It is uncertain whether this is related to total body fat or other factors that correlate with body mass index. We aimed to quantify the association between total body fat (measured by bioelectrical impedance) and risk of BO and examine if this association was modified by gastro-oesophageal reflux (GOR) and abdominal obesity. MethodsIn 2007–2009, we surveyed 235 cases (69% Males, Mean age 62.1 years) and 244 age and sex matched population controls from a population based case–control study of BO. We conducted structured interviews, standard anthropometry and bioimpedance analysis of total body fat. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression analysis. ResultsThere was a significantly increased risk of BO among those in the highest tertile of total body fat weight (OR 2.01; 95%CI 1.26–3.21) and total body fat percentage (OR 1.86; 95%CI 1.10–3.15). These risks were largely attenuated after adjustment for GOR and waist circumference. There was a significantly increased risk of BO among those in the highest tertile of waist circumference (OR 2.21; 95%CI 1.39–3.51) and this was minimally attenuated after adjustment for total body fat and moderately attenuated after adjustment for GOR. ConclusionsTotal body fat is associated with an increased risk of BO but this appears to be mediated via both abdominal obesity and GOR. These findings provide evidence that abdominal obesity is more important than total body fat in the development of BO.

Vegetable, fruit and nitrate intake in relation to the risk of Barrett's oesophagus in a large Dutch cohort

There are few epidemiological data on the dietary risk factors of Barrett's oesophagus, a precursor of oesophageal adenocarcinoma. The present study investigated the association between vegetable, fruit and nitrate intake and Barrett's oesophagus risk in a large prospective cohort. The Netherlands Cohort Study recruited 120,852 individuals aged 55-69 years in 1986. Vegetable and fruit intake was assessed using a 150-item FFQ, and nitrate intake from dietary sources and drinking water was determined. After 16.3 years of follow-up, 433 cases (241 men and 192 women) of Barrett's oesophagus with specialised intestinal metaplasia and 3717 subcohort members were analysed in a case-cohort design using Cox proportional hazards models while adjusting for potential confounders. Men exhibited a lower risk of Barrett's oesophagus in the highest v. the lowest quintile of total (multivariable-adjusted hazard ratio (HR): 0.66, 95% CI 0.43, 1.01), raw (HR 0.63, 95% CI 0.40, 0.99), raw leafy (HR 0.55, 95% CI 0.36, 0.86) and Brassica (HR 0.64, 95% CI 0.41, 1.00) vegetable intake. No association was found for other vegetable groups and fruits. No significant associations were found between vegetable and fruit intake and Barrett's oesophagus risk among women. Total nitrate intake was inversely associated with Barrett's disease risk in men (HR 0.50, 95% CI 0.25, 0.99) and positively associated with it in women (HR 3.77, 95% CI 1.68, 8.45) (P for interaction = 0.04). These results suggest that vegetable intake may contribute to the prevention of Barrett's oesophagus. The possible differential effect in men and women should be evaluated further.

Risk factors and chemoprevention in Barrett's esophagus – an update

Objective. Barrett's esophagus (BO) is a precursor of esophageal adenocarcinoma (OAC), a cancer with a poor prognosis and an increasing incidence. Hence there is an interest in mapping causal factors underlying BO and finding strategies to reduce the risk of dysplasia progression in patients with BO. Here we review current knowledge on established as well as less risk factors for the development of BO. Additionally, we summarize today's status on the use of chemoprevention aiming to reduce the risk of cancer progression in BO patients. Methods.We searched Medline and the Cochrane Library using the MeSH terms “Barrett's esophagus” and “Barrett esophagus,” both alone and combined with the terms “risk factor,” “aetiology,” “diet,” or “prevention.” Focus was on original contributions, systematic reviews, and meta-analyses. Results. Established risk factors for the development of BO include gastro-esophageal reflux, obesity, male gender, Caucasian ethnicity, and increasing age. Smoking might increase the risk of BO, while aspirin/NSAIDs, Helicobacter pylori infection, and specific “healthy” dietary factors may lower the risk. The potential value of using chemoprevention with proton pump inhibitors, aspirin/NSAIDs, or statins is still uncertain. Conclusions.There is today a substantial knowledge of risk factors of BO. Certain diet may be protective of BO, albeit yet to be proven. The efficiency of chemoprevention in BO is currently addressed further in randomized clinical trials.

Association of insulin and insulin-like growth factors with Barrett's oesophagus

BackgroundIt is postulated that high serum levels of insulin and insulin growth factor 1 (IGF-1) mediate obesity-associated carcinogenesis. The relationship of insulin, IGF-1 and IGF binding proteins (IGFBP) with Barrett's...

PTH-061 Vitamin D is associated with an increased risk of oesophageal adenocarcinoma but not its pre-cursor conditions

Introduction Evidence is accumulating that vitamin D may be protective against the development of many cancers.[1][1] There are notable exceptions in the literature though, demonstrating increased risks of oesophageal squamous cell carcinoma and oesophageal squamous dysplasia for individuals with the highest serum concentrations of 25-hydroxyvitamin D.[2][2] ,[3][3] Our aim was to explore the association between dietary vitamin D and related nutrients and the risk of oesophageal adenocarcinoma (OAC) and its pre-cursor conditions, Barrett's oesophagus (BO) and reflux oesophagitis (RO). Methods In an all-Ireland case-control study conducted between March 2002 and July 2005, 218 OAC patients, 212 long-segment BO patients, 208 RO patients and 252 healthy population-based controls completed a 101-item food frequency questionnaire, in addition to providing other lifestyle information and medical histories. Multiple logistic regression analysis was applied to examine the association between vitamin D, calcium and dairy intake and disease risk, prior to and after adjustment for potential confounders. Stratified analyses were also conducted by body mass index status. Results OAC risk was significantly greater for individuals in the highest compared with the lowest tertile of vitamin D intake (OR 1.99, 95% CI 1.03 to 3.86, p for trend=0.02) after adjustment for potential confounders. This elevated risk appeared to be accentuated in overweight (OR 2.49, 95% CI 1.16 to 5.37) OAC patients, although formal tests for interaction were not significant. Vitamin D intake was unrelated to RO and BO risk. There were no significant associations observed for calcium or dairy intake and RO, BO or OAC risk. Conclusion A significant direct association was observed between vitamin D intake and OAC risk, which concurs with previous findings for oesophageal squamous cell carcinoma. Vitamin D intake was unrelated to RO and BO risk. No significant associations were found between calcium or dairy intake and the risk of these oesophageal lesions. Further research is needed before recommendations to establish dietary vitamin D guidelines are implemented. [1]: #ref-1 [2]: #ref-2 [3]: #ref-3

P26 Non-steroidal anti-inflammatory drug use, a common cyclooxygenase-2 polymorphism (T8473C), and risk for Barrett esophagus

TP53 mutation is associated with various hematological malignancies and immunohistochemistry of p53 has been used as a simple method to establish the presence of a TP53 mutation. Since the significance of p53 expression is controversial in myelodysplastic syndrome (MDS) patients treated with azacitidine (Aza), we analyzed the prevalence of p53 expression as a prognostic factor in 60 MDS patients treated with Aza. To assess p53 expression, immunohistochemical analyses of bone marrow clot sections were performed. Overall survival (OS) was significantly lower in p53-positive patients compared with p53-negetive patients (59% vs. 85% at 12 months; P = 0.006). Multivariate analysis demonstrated that p53-positive was a significant prognostic factor for OS along with poor cytogenetics. Here, we propose a new prognostic index to make short-term prognoses of MDS patients in the era of Aza treatment; high: p53-positive and poor cytogenetics, low: p53-negative and absence of poor cytogenetics, and intermediate: the others. OS was significantly different among the three groups according to this index (Low 92%, Intermediate 65% and High 27% at 12 months; P < 0.0001). In conclusion, p53 expression was a significant prognostic factor in MDS patients treated with Aza. In combination with cytogenetic abnormalities, it is possible to make short-term prognoses.