Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Sep 30;106(11):dju252.
doi: 10.1093/jnci/dju252. Print 2014 Nov.

Obesity and risk of esophageal adenocarcinoma and Barrett's esophagus: a Mendelian randomization study

Aaron P Thrift  1 , Nicholas J Shaheen  2 , Marilie D Gammon  2 , Leslie Bernstein  2 , Brian J Reid  2 , Lynn Onstad  2 , Harvey A Risch  2 , Geoffrey Liu  2 , Nigel C Bird  2 , Anna H Wu  2 , Douglas A Corley  2 , Yvonne Romero  2 , Stephen J Chanock  2 , Wong-Ho Chow  2 , Alan G Casson  2 , David M Levine  2 , Rui Zhang  2 , Weronica E Ek  2 , Stuart MacGregor  2 , Weimin Ye  2 , Laura J Hardie  2 , Thomas L Vaughan  2 , David C Whiteman  2
Affiliations

Obesity and risk of esophageal adenocarcinoma and Barrett's esophagus: a Mendelian randomization study

Aaron P Thrift et al. J Natl Cancer Inst. .

Abstract

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.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Distribution of the unweighted genetic risk score (left y-axis and histogram) and mean body mass index by genetic risk score and case-control status (right y-axis and marks). BE = Barrett’s esophagus; EAC = esophageal adenocarcinoma.
See this image and copyright information in PMC

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Thrift AP, Whiteman DC. The incidence of esophageal adenocarcinoma continues to rise: analysis of period and birth cohort effects on recent trends. Ann Oncol. 2012;23(12):3155–3162 - PubMed
    1. Edgren G, Adami HO, Weiderpass E, Nyren O. A global assessment of the oesophageal adenocarcinoma epidemic. Gut. 2013;62(10):1406–1414 - PubMed
    1. American Cancer Society. Cancer Facts and Figures 2012. Atlanta: American Cancer Society; 2012
    1. Surveillance Epidemiology and End Results (SEER) Program. Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) SEER*Stat Database: Incidence - SEER 9 Regs Research Data, Nov 2011 Sub (1973–2010) <Katrina/Rita Population Adjustment> - Linked To County Attributes - Total U.S., 1969–2010 Counties, National Cancer Institute, DCCPS, Surveillance Research Program, Surveillance Systems Branch, released April 2013, based on the November 2012 submission. 2012.
    1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127(12):2893–2917 - PubMed

Publication types

MeSH terms