@article{cb0be9555909450f851329db9e9973e8,
title = "Obesity and risk of esophageal adenocarcinoma and barrett's esophagus: A mendelian randomization study",
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 1 kg/m2 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.",
author = "{Mayo Clinic Esophageal Adenocarcinoma and Barrett's Esophagus Registry Consortium} and Alberts, {Steven R.} and Ashman, {Jonathan Ben} and Boardman, {Lisa A.} and Bouras, {Ernest Peter} and Buttar, {Navtej S.} and Camoriano, {John K.} and Stephen Cassivi and Crowell, {Michael D} and Cunningham, {Julie M.} and {De Andrade}, Mariza and {De Groen}, {Piet C} and Diasio, {Robert B.} and DiBaise, {John K.} and Edell, {Eric S.} and Charles Erlichman and Faigel, {Douglas O.} and Fitch, {Tom Robert} and Fleischer, {David E} and Foxx-Orenstein, {Amy Elisabeth} and Evanthia Galanis and Grothey, {Axel F} and Haddock, {Michael G.} and Halling, {Kevin Carl} and Harnois, {Denise M.} and Timothy Hobday and Houghton, {Lesley A} and Iyer, {Prasad A.} and Jaroszewski, {Dawn E} and Aminah Jatoi and Jenkins, {Robert B.} and Katzka, {David A} and Keaveny, {Andrew P} and Dora Lam-Himlin and Limburg, {Paul J.} and Lingle, {Wilma L} and Locke, {Giles Richard III} and Martenson, {James A Jr.} and McWilliams, {Robert R.} and Miller, {Robert Clell} and Murray, {Joseph A.} and Nguyen, {Cuong C.} and Rahul Pannala and Harshita Paripati and Parker, {Alexander S.} and Pasha, {Shabana F.} and Petersen, {Bret T.} and Petersen, {Gloria M.} and Picco, {Michael F} and Pitot, {Henry C.} and Massimo Raimondo and Ramirez, {Francisco Pancho C.} and Ross, {Helen J} and Sargent, {Daniel Jay} and Schaid, {Daniel J.} and Qian Shi and Sinicrope, {Frank A.} and Sloan, {Jeff A} and Smith, {David I} and Smyrk, {Thomas Christopher} and Thibodeau, {Stephen N.} and Wallace, {Michael B.} and Wang, {Kenneth K.} and Weinshilboum, {Richard M.} and Dennis Wigle and Wolfsen, {Herbert C} and {Wong Kee Song}, {Louis Michel} and Woodward, {Timothy A} and Wu, {Tsung The} and Yoon, {Harry H.} and Zinsmeister, {Alan R}",
note = "Publisher Copyright: {\textcopyright} The Author 2014.",
year = "2014",
month = nov,
day = "1",
doi = "10.1093/jnci/dju252",
language = "English (US)",
volume = "106",
journal = "Journal of the National Cancer Institute",
issn = "0027-8874",
publisher = "Oxford University Press",
number = "11",
}