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Abdominal fat raises risk for esophageal disease and cancer

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High central adiposity a greater risk than high BMI

Over the past several decades, obesity has reached epidemic proportions in the United States. Obesity is associated with an increased risk of several gastrointestinal malignancies, including esophageal adenocarcinoma. Body mass index (BMI), calculated as a function of height and weight, is the measure traditionally used to estimate obesity in studies of disease association. While increased BMI is generally associated with a modest increased risk of esophageal adenocarcinoma, associations with Barrett's esophagus have been inconsistent. However, it may be more important to focus on central adiposity, as visceral fat produces many proinflammatory cytokines (or adipokines) that in turn may have cancer-promoting effects.

Dr. Julian Abrams

In fact, recent studies that have used measures of central adiposity such as waist-to-hip ratio (WHR) have reported more-consistent associations with an increased risk of esophageal neoplasia. Singh et al. performed an excellent meta-analysis of these studies and found a nearly twofold increased risk of esophagitis, Barrett's esophagus, and esophageal adenocarcinoma. Furthermore, this association persisted even after adjusting for BMI, suggesting that the association between obesity and esophageal neoplasia is largely mediated by central adiposity.

Based on these results, future studies of obesity and Barrett's esophagus and esophageal adenocarcinoma should focus on central adiposity, as estimated by WHR, CT volumetric analysis, or some other means. Additionally, research should be aimed at understanding how visceral fat contributes to the development of esophageal adenocarcinoma and whether we can implement measures specifically targeted at reducing visceral fat to lower EAC risk.

Dr. Julian Abrams is the Florence Irving Assistant Professor of Medicine in the division of digestive and liver diseases, Columbia University Medical Center, New York. He has no conflicts of interest to report.


 

FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY

Excess abdominal fat increases the risk for both Barrett’s esophagus and erosive esophagitis even after body mass index is accounted for, according to a recent meta-analysis. Extra fat around the middle also increases the risk for esophageal adenocarcinoma.

"Central adiposity has a strong and consistent association with development of esophageal inflammation, metaplasia, and neoplasia, independent of BMI [body mass index]," reported Dr. Siddharth Singh and his colleagues in the November issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2013.05.009). "In addition, central adiposity may be more highly associated with a reflux-independent effect on the development of Barrett’s esophagus and perhaps explains the predominance of esophageal adenocarcinoma in this population," said Dr. Singh of the Mayo Clinic in Rochester, Minn., and his coauthors.

Dr. Siddharth Singh

The researchers conducted a systematic review and meta-analysis of all studies published through March 2013 in PubMed, Embase, or Web of Science that investigated associations between central adiposity and the risk of erosive esophagitis, Barrett’s esophagus, or esophageal adenocarcinoma. Included studies used computed tomography, waist-hip ratio, or waist circumference to assess central adiposity or visceral adipose tissue area or volume.

The researchers identified 40 studies, including 19 on erosive esophagitis, 17 on Barrett’s esophagus, and 6 on esophageal adenocarcinoma (including studies of overlapping conditions). Of the 37 independent populations covered in these studies, 18 involved Asian populations and the rest involved Western populations.

Compared with study participants in the lowest body-type category, participants with the highest central adiposity had 1.87 greater odds of erosive esophagitis, based on analysis of 18 heterogeneous studies (adjusted odds ratio, 1.87; 95% CI, 1.51-2.31). When the researchers analyzed only the eight studies that controlled for BMI, the risk remained (aOR, 1.93; 95% CI, 1.38-2.71). Although the researchers lacked data to assess the influence of gastroesophageal reflux disease (GERD) symptoms, they did find a dose-response relationship for higher central adiposity and higher erosive esophagitis risk.

An analysis of 15 studies similarly showed a greater risk for Barrett’s esophagus with greater central adiposity – even after accounting for BMI – and a dose-response relationship. Compared with participants in the lowest category of central adiposity, those in the highest group had about double the odds of Barrett’s esophagus (aOR, 1.98; 95% CI, 1.52-2.57). When the researchers evaluated Barrett’s esophagus risk in the five studies that allowed for BMI adjustment, the risk remained high (aOR, 1.88; 95% CI, 1.20-2.95).

In the 11 Barrett’s esophagus studies that controlled for GERD or used control-group participants with GERD, abdominal fat still doubled the odds for Barrett’s esophagus (aOR, 2.04; 95% CI, 1.44-2.90). Meanwhile, overall obesity had no impact on Barrett’s esophagus risk (aOR, 1.15; 95% CI, 0.89-1.47).

Even when the investigators analyzed only the seven studies in which GERD patients without Barrett’s esophagus were compared to Barrett’s esophagus patients, they found an increased risk of central adiposity (aOR, 2.51; 95% CI, 1.48-4.25). Meanwhile, BMI showed no effect on risk in these studies (aOR, 1.23; 95% CI, 0.90-1.66). "These results suggest that central adiposity, rather than overall obesity, may have a GERD symptom-independent effect on development of esophageal metaplasia," the researchers wrote.

The six studies on esophageal adenocarcinoma revealed an increased risk for the cancer with increased abdominal adiposity (aOR, 2.51; 95% CI, 1.56-4.04), though too little data existed to evaluate a dose-response relationship or to calculate risk independent of BMI or GERD symptoms.

For all these analyses, data on the following confounders was also included when available: "age, sex, race, BMI, smoking status, alcohol consumption, GERD symptoms, use of proton pump inhibitors or histamine receptor antagonists, presence of hiatal hernia, family history of esophageal adenocarcinoma, caffeine intake, Helicobacter pylori infection, use of putative chemopreventive agents (aspirin, nonsteroidal anti-inflammatory drugs, statins), and for studies reporting EAC [esophageal adenocarcinoma] as outcome, presence, length, and histology of Barrett’s esophagus."

The authors suggested several possible reasons for the findings, starting with the higher risk for reflux that exists with more abdominal fat. They also noted that abdominal fat may cause systemic or inflammatory effects that could lead to Barrett’s esophagus and cancer, whether independently or in conjunction with other factors.

Past research has already shown an increased risk for colon and pancreatic cancer resulting from visceral fat’s "adipocytokine-mediated carcinogenic effect," the researchers wrote. They also noted the link between abdominal fat and insulin resistance and pointed out that recent research has found evidence for the "role of the insulin–insulin growth factor-1 axis in promoting esophageal neoplasia."

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the American College of Gastroenterology. The authors had no disclosures.

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