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Clin Gastroenterol Hepatol. 2014 Oct;12(10):1667-76.e1. doi: 10.1016/j.cgh.2014.01.039. Epub 2014 Feb 12.

Risk of esophageal adenocarcinoma decreases with height, based on consortium analysis and confirmed by mendelian randomization.

Author information

  • 1Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington; Cancer Control Group, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. Electronic address: athrift@fhcrc.org.
  • 2Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut.
  • 3Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • 4Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
  • 5Department of Surgery, University of Saskatchewan, Saskatoon, Canada.
  • 6Department of Population Sciences, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, California.
  • 7Division of Research and Oakland Medical Center, Kaiser Permanente, Oakland, California.
  • 8Department of Biostatistics, University of Washington School of Public Health, Seattle, Washington.
  • 9Department of Epidemiology, MD Anderson Cancer Center, Houston, Texas.
  • 10Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington; Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • 11Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
  • 12Division of Epidemiology, University of Leeds, Leeds, United Kingdom.
  • 13Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre-Ontario Cancer Institute, University of Toronto, Toronto, Ontario, Canada.
  • 14Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, California.
  • 15Department of Oncology, The Medical School, University of Sheffield, United Kingdom.
  • 16Department of Epidemiology, University of North Carolina School of Public Health, Chapel Hill, North Carolina.
  • 17Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • 18Cancer Control Group, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.

Abstract

BACKGROUND & AIMS:

Risks for some cancers increase with height. We investigated the relationship between height and risk of esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE).

METHODS:

We analyzed epidemiologic and genome-wide genomic data from individuals of European ancestry in the Barrett's and Esophageal Adenocarcinoma Consortium, from 999 cases of EAC, 2061 cases of BE, and 2168 population controls. Multivariable logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for associations between height and risks of EAC and BE. We performed a Mendelian randomization analysis to estimate an unconfounded effect of height on EAC and BE using a genetic risk score derived from 243 genetic variants associated with height as an instrumental variable.

RESULTS:

Height was associated inversely with EAC (per 10-cm increase in height: OR, 0.70; 95% CI, 0.62-0.79 for men and OR, 0.57; 95% CI 0.40-0.80 for women) and BE (per 10-cm increase in height: OR, 0.69; 95% CI, 0.62-0.77 for men and OR, 0.61; 95% CI, 0.48-0.77 for women). The risk estimates were consistent across strata of age, education level, smoking, gastroesophageal reflux symptoms, body mass index, and weight. Mendelian randomization analysis yielded results quantitatively similar to those from the conventional epidemiologic analysis.

CONCLUSIONS:

Height is associated inversely with risks of EAC and BE. Results from the Mendelian randomization study showed that the inverse association observed did not result from confounding factors. Mechanistic studies of the effect of height on EAC and BE are warranted; height could have utility in clinical risk stratification.

Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

KEYWORDS:

Esophageal Cancer; Etiology; Risk Factors; Sex Differences

PMID:
24530603
[PubMed - in process]
PMCID:
PMC4130803
[Available on 2015-10-01]
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