Clin Gastroenterol Hepatol. 2014 Feb 12. pii: S1542-3565(14)00199-2. doi: 10.1016/j.cgh.2014.01.039. [Epub ahead of print]

Risk of Esophageal Adenocarcinoma Decreases with Height, Based on Consortium Analysis and Confirmed by Mendelian Randomization.

Thrift AP, Risch HA, Onstad L, Shaheen NJ, Casson AG, Bernstein L, Corley DA, Levine DM, Chow WH, Reid BJ, Romero Y, Hardie LJ, Liu G, Wu AH, Bird NC, Gammon MD, Ye W, Whiteman DC, Vaughan TL.

See story in Fred Hutchinson Center News

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 inversely associated 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.

height spline

CONCLUSIONS:Height is inversely associated with risks of EAC and BE. Results from the Mendelian randomization study demonstrated 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.