title: Risk of esophageal adenocarcinoma decreases with height, based on consortium analysis and confirmed by Mendelian randomization.
abstract: OBJECTIVE
  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.
authors: Division 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.
authors: Aaron P
authors: AP
authors: Thrift
authors: Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut.
authors: Harvey A
authors: HA
authors: Risch
authors: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: Lynn
authors: L
authors: Onstad
authors: Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors: Nicholas J
authors: NJ
authors: Shaheen
authors: Department of Surgery, University of Saskatchewan, Saskatoon, Canada.
authors: Alan G
authors: AG
authors: Casson
authors: Department of Population Sciences, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, California.
authors: Leslie
authors: L
authors: Bernstein
authors: Division of Research and Oakland Medical Center, Kaiser Permanente, Oakland, California.
authors: Douglas A
authors: DA
authors: Corley
authors: Department of Biostatistics, University of Washington School of Public Health, Seattle, Washington.
authors: David M
authors: DM
authors: Levine
authors: Department of Epidemiology, MD Anderson Cancer Center, Houston, Texas.
authors: Wong-Ho
authors: WH
authors: Chow
authors: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington; Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: Brian J
authors: BJ
authors: Reid
authors: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
authors: Yvonne
authors: Y
authors: Romero
authors: Division of Epidemiology, University of Leeds, Leeds, United Kingdom.
authors: Laura J
authors: LJ
authors: Hardie
authors: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre-Ontario Cancer Institute, University of Toronto, Toronto, Ontario, Canada.
authors: Geoffrey
authors: G
authors: Liu
authors: Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, California.
authors: Anna H
authors: AH
authors: Wu
authors: Department of Oncology, The Medical School, University of Sheffield, United Kingdom.
authors: Nigel C
authors: NC
authors: Bird
authors: Department of Epidemiology, University of North Carolina School of Public Health, Chapel Hill, North Carolina.
authors: Marilie D
authors: MD
authors: Gammon
authors: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors: Weimin
authors: W
authors: Ye
authors: Cancer Control Group, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors: David C
authors: DC
authors: Whiteman
authors: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: Thomas L
authors: TL
authors: Vaughan
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000453:epidemiology; D001827:Body Height; D004938:Esophageal Neoplasms / Q000453:epidemiology*; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D008297:Male; D057182:Mendelian Randomization Analysis; D008875:Middle Aged; D012307:Risk Factors
keywords: Esophageal Cancer; Etiology; Risk Factors; Sex Differences