Is Obesity Associated with Barrett’s Esophagus and Esophageal Adenocarcinoma?

Barrett’s esophagus is a premalignant condition portending increased risk of esophageal adenocarcinoma. Given the significant morbidity and mortality of esophageal adenocarcinoma, identification of risk factors for Barrett’s esophagus and esophageal adenocarcinoma is crucial. There are a plethora of studies investigating the relationship of obesity with these pathologies. Recent studies reveal that this relationship may specifically be with central adiposity. Increased cell turnover and eventual carcinogenesis is likely precipitated by increased intragastric pressure but also is affected by the complex interplay of increased insulin resistance in patients with increased fat tissue. Further studies are warranted to evaluate if weight loss can decrease progression of Barrett’s esophagus.

Key points

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Barrett’s esophagus is characterized by metaplastic columnar epithelium in the distal esophagus. Esophageal adenocarcinoma can occur from dysplastic progression of Barrett’s esophagus.
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There is evidence that Barrett’s esophagus is more strongly related to central adiposity and waist-to-hip-ratio than overall obesity.
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Both obesity and the incidence of esophageal adenocarcinoma have increased significantly in the past three decades. Numerous studies have shown an association between obesity and esophageal adenocarcinoma.
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The mechanism by which obesity leads to carcinogenesis involves a complex interplay of inflammatory cytokines and hormones.
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Further studies are warranted to investigate whether weight loss can decrease the risk of Barrett’s esophagus and progression to esophageal adenocarcinoma.

Introduction

The incidence of Barrett’s esophagus and esophageal adenocarcinoma (EAC) has increased over the past several decades in the Western world. The rise in obesity paralleled this increase. It is known that obesity predisposes to many different types of malignancy; EAC is one such malignancy. Barrett’s esophagus is a recent area of investigation given that it is a precursor lesion to EAC. One may assume that Barrett’s esophagus shares risk factors with EAC and thus has the same relationship with obesity. However, not all patients with Barrett’s esophagus develop esophageal malignancy so its risk factors may be unique. The treatment of Barrett’s esophagus is currently still in evolution and the identification of modifiable risk factors for Barrett’s esophagus is crucial in prevention and risk stratification. This article investigates the relationship between obesity and Barrett’s esophagus and EAC.

Introduction

The incidence of Barrett’s esophagus and esophageal adenocarcinoma (EAC) has increased over the past several decades in the Western world. The rise in obesity paralleled this increase. It is known that obesity predisposes to many different types of malignancy; EAC is one such malignancy. Barrett’s esophagus is a recent area of investigation given that it is a precursor lesion to EAC. One may assume that Barrett’s esophagus shares risk factors with EAC and thus has the same relationship with obesity. However, not all patients with Barrett’s esophagus develop esophageal malignancy so its risk factors may be unique. The treatment of Barrett’s esophagus is currently still in evolution and the identification of modifiable risk factors for Barrett’s esophagus is crucial in prevention and risk stratification. This article investigates the relationship between obesity and Barrett’s esophagus and EAC.

Barrett’s esophagus

Barrett’s esophagus is characterized by the replacement of squamous mucosa in the distal esophagus with metaplastic columnar epithelium as a result of chronic exposure of the distal esophagus to acidic gastric contents. Barrett’s esophagus can progress to low-grade dysplasia and high-grade dysplasia before ultimately terminating in EAC seen in Fig. 1 . However, this pathway is not obligatory. Nevertheless, Barrett’s esophagus is associated with a 40-fold increase in the risk of EAC over the general population. Thus, the identification of risk factors for Barrett’s metaplasia is crucial in attempts to prevent the disease and optimizing treatment selection.

Obesity and Barrett’s esophagus

Epidemiologic studies have revealed that the mean body mass index (BMI) is higher in patients with Barrett’s esophagus than the general population. Follow-up cross-sectional studies have demonstrated a significant relationship between Barrett’s esophagus and obesity. Additionally, it has been shown that increased BMI is associated more strongly with long-segment than short-segment Barrett’s esophagus. Therefore, obesity may be a risk factor for Barrett’s metaplasia and a possible factor in furthering the progression of metaplasia toward malignancy.

However, recent works suggest that central adiposity may be a more important risk factor for Barrett’s esophagus than simply BMI. BMI is clearly not applicable to every patient because it only takes into account weight and height, not necessarily body composition. A population-based study of Washington state residents found that a high waist-to-hip ratio was strongly related to Barrett’s esophagus risk (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.5–5.1) but the association between BMI and Barrett’s esophagus was not as strong (OR, 1.5; 95% CI, 0.8–2.9). Adjustment for heartburn symptoms did not significantly change this result, suggesting that this relationship may be independent of gastroesophageal reflux disease (GERD).

Abdominal circumference has also been identified as a more precise potential risk factor for Barrett’s esophagus. A case control study found a significant association between larger abdominal circumference and Barrett’s esophagus (OR, 2.24; 95% CI, 1.21–4.15) and no association with BMI. Factoring in GERD symptoms somewhat attenuated the results, giving an adjusted OR of 1.78 (95% CI, 0.86–3.66). A later case control study revealed similar results; patients with Barrett’s esophagus were twice as likely to have a high waist-to-hip ratio as control patients but mean BMI was unrelated. This association between Barrett’s esophagus and waist-to-hip ratio was not significantly attenuated when GERD symptoms were factored in.

Finally, a recent meta-analysis found an association between central adiposity and Barrett’s esophagus that persisted after adjusting for BMI. This analysis showed that after adjusting for GERD symptoms, patients with central adiposity had double the risk of Barrett’s esophagus than those without central adiposity. A summary of the prior studies evaluating central adiposity and obesity in relation to Barrett’s esophagus is seen in Fig. 2 . As displayed, central adiposity indeed seems to be more strongly related to Barrett’s esophagus than overall obesity.

Obesity and esophageal adenocarcinoma

The incidence of EAC has increased a staggering 600% over the last 30 years. At the same time, the worldwide prevalence of obesity has also increased. Fig. 3 shows the trends in incidence of EAC and in obesity prevalence. Given the increase in obesity and EAC in the past several decades, numerous studies have examined this relationship. A study based on registry data examined the increase in EAC in the United States, Spain, and the Netherlands. There was a significant increase in all three countries and most significantly in the Netherlands. However, the increase in obesity in these countries over the same time period did not precisely parallel the rise in EAC. Thus it was thought that these trends were not necessarily related.