Obesity Drives Malignant Progression of Barrett’s Esophagus

Obesity appears to be associated with malignant progression of Barrett’s esophagus (BE), according to a recent systematic review and meta-analysis.

A dose-response relationship exists between body mass index (BMI) and esophageal adenocarcinoma (EAC) or high-grade dysplasia (HGD), the authors found.

“Obesity has been implicated in the pathogenesis of many reflux-related esophageal disorders such as gastroesophageal reflux disease (GERD), BE, and EAC,” said senior author Leo Alexandre, MRCP, PhD, a clinical associate professor and member of the Norwich Epidemiology Centre at the University of East Anglia and gastroenterologist with the Norfolk & Norwich University Hospital NHS Foundation Trust, both in Norwich, England.

“Guidelines advocate obesity as a criterion for targeted screening for BE in patients with chronic reflux symptoms,” he said. “While obesity is a recognized risk factor for both BE and EAC, it’s been unclear whether obesity is a risk factor for malignant progression.”

The study was published in Clinical Gastroenterology and Hepatology.

Analyzing Risk

BE, which is the only recognized precursor lesion to EAC, is associated with a 30-fold increase in the incidence of the aggressive cancer. Typically, malignant progression occurs when nondysplastic BE epithelium progresses to low-grade dysplasia (LGD) and then HGD, followed by invasive adenocarcinoma.

Current guidelines suggest that patients with BE undergo endoscopic surveillance for early detection of adenocarcinoma. However, clinical risk factors could help with risk stratification and a personalized approach to long-term BE management, the authors wrote.

Alexandre and colleagues reviewed case-control or cohort studies that reported on the effect of BMI on the progression of nondysplastic BE or LGD to EAC, HGD, or esophageal cancer (EC). Then they estimated the dose-response relationship with a two-stage dose-response meta-analysis.

Overall, 20 observational studies reported data on 38,565 adult patients, including 1684 patients who were diagnosed with EAC, HGD, or EC. The studies enrolled patients between 1976 and 2019 and were published between 2005 and 2022. Most were based in Europe or the United States, and 74.4% of participants were men.

Among 12 cohort studies with 19,223 patients who had baseline nondysplastic BE or LGD, 816 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .03%.

Among eight cohort studies with 6647 male patients who had baseline nondysplastic BE or LGD, 555 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .02%.

In addition, among 1992 female patients with baseline nondysplastic BE or LGD, 110 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .01%, which wasn’t a significant difference compared with the progression rate among male patients.

Based on meta-analyses, obesity was associated with a 4% increase in the risk for malignant progression among patients with BE (unadjusted odds ratio, 1.04; 95% CI, 1.00-1.07; P

Notably, each 5 unit increase in BMI was associated with a 6% increase in the risk of developing HGD or EAC (adjusted odds ratio, 1.06; 95% CI, 1.02-1.10; P

“Although the exact mechanisms by which obesity promotes esophageal carcinogenesis is not fully understood, several possible mechanisms may explain it,” Alexandre said. “The most obvious pathologic link is via GERD, with the mechanical effect of visceral obesity promoting the GERD directly, and the sequence of Barrett’s dysplasia to cancer indirectly. In addition, it has been demonstrated in experimental studies that gastric acid and bile acid drive malignant changes in esophageal epithelium through stimulation of proliferation, inhibition of apoptosis, and generation of free radicals.”

Considering Risk

This study highlights the importance of recognizing the association between obesity and cancer risks, said Prateek Sharma, MD, professor of medicine and director of gastrointestinal training at the University of Kansas School of Medicine, Kansas City, Kansas.

Sharma, who wasn’t involved with this study, coauthored an American Gastroenterological Association technical review on the management of BE.

“Obesity is a known risk factor for esophageal adenocarcinoma and may be a modifiable risk factor,” he said. “Showing that BMI is related to neoplastic progression in Barrett’s esophagus may impact surveillance intervals.”

Future research should look at additional obesity-related factors, such as visceral obesity and malignant progression of BE, as well as whether diet, lifestyle, and bariatric interventions can reduce the risk for progression.

“The next steps also include plugging BMI into risk scores and risk stratification models to enable targeted surveillance among high-risk groups,” Sharma said.

One of the study coauthors received funding as a National Institute for Health Research Academic clinical fellow. No other funding sources were declared. Alexandre and Sharma reported no relevant disclosures.

Carolyn Crist is a health and medical journalist who reports on the latest studies for Medscape Medical News, MDedge, and WebMD.