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Updated: Apr 23, 2026
An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells
Published on: July 20, 2014
Obesity and risk of esophageal adenocarcinoma and Barrett's esophagus: a Mendelian randomization study
Aaron P Thrift1, Nicholas J Shaheen2, Marilie D Gammon2
1Division of Public Health Sciences (APT, LO, TLV) and Division of Human Biology (BJR), Fred Hutchinson Cancer Research Center, Seattle, WA; Cancer Control Group (APT, DCW) and Statistical Genetics (WEE, SM), QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Division of Gastroenterology and Hepatology, UNC School of Medicine (NJS) and Department of Epidemiology, School of Public Health (MDG), University of North Carolina, Chapel Hill, NC; Department of Population Sciences, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, CA (LB); Yale School of Public Health, Department of Chronic Disease Epidemiology, New Haven, CT (HAR); Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre-Ontario Cancer Institute, University of Toronto, Toronto, ON, Canada (GL); Department of Oncology, The Medical School, University of Sheffield, Sheffield, UK (NCB); Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA (AHW); Division of Research and Oakland Medical Center, Kaiser Permanente, Oakland, CA (DAC); Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN (YR), on behalf of the Mayo Clinic Esophageal Adenocarcinoma and Barrett's Esophagus Registry Consortium; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (SJC); Department of Epidemiology, MD Anderson Cancer Center, Houston, TX (WHC); Department of Surgery, University of Saskatchewan, Saskatoon SK, Canada (AGC); Department of Biostatistics, University of Washington School of Public Health, Seattle, WA (DML, RZ); Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (WY); Division of Epidemiology, University of Leeds, Leeds, UK (LJH). athrift@fhcrc.org.
Background:
Data from observational studies suggest that body mass index (BMI) is causally related to esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE). However, the relationships may be affected by bias and confounding.
Methods:
We used data from the Barrett's and Esophageal Adenocarcinoma Genetic Susceptibility Study: 999 patients with EAC, 2061 patients with BE, and 2169 population controls. We applied the two-stage control function instrumental variable method of the Mendelian randomization approach to estimate the unbiased, unconfounded effect of BMI on risk of EAC and BE. This was performed using a genetic risk score, derived from 29 genetic variants shown to be associated with BMI, as an instrument for lifetime BMI. A higher score indicates propensity to obesity. All tests were two-sided.
Results:
The genetic risk score was not associated with potential confounders, including gastroesophageal reflux symptoms and smoking. In the instrumental variable analyses (IV), EAC risk increased by 16% (IV-odds ratio [OR] = 1.16, 95% confidence interval [CI] = 1.01 to 1.33) and BE risk increased by 12% (IV-OR = 1.12, 95% CI = 1.00 to 1.25) per 1kg/m(2) increase in BMI. BMI was statistically significantly associated with EAC and BE in conventional epidemiologic analyses.
Conclusions:
People with a high genetic propensity to obesity have higher risks of esophageal metaplasia and neoplasia than people with low genetic propensity. These analyses provide the strongest evidence to date that obesity is independently associated with BE and EAC, and is not due to confounding or bias inherent in conventional epidemiologic analyses.
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