BACKGROUND: To investigate potential biologic mechanisms underlying the association between obesity and risk for esophageal adenocarcinoma (EADC), we studied the frequency of a common polymorphism of the insulin-like growth factor I receptor (IGF-IR) gene in patients with either gastroesophageal reflux disease (GERD), premalignant Barrett esophagus (BE) and or invasive EADC. METHODS: Using a well characterized series of 431 individuals enrolled in a case-control study, we studied the frequency of the IGF-IR gene polymorphism, G1013A. RESULTS: On multivariate analysis controlling for age and gender, in comparison to asymptomatic controls, obese individuals with the polymorphic A-variant (G/A, A/A) were found to have significantly increased risk for EADC (OR 4.81; 95%CI 1.09-21.15), whereas obese individuals with the G/G variant were not at statistically significant increased risk (OR 2.69; 95%CI 0.41-17.62). Similarly, compared to asymptomatic controls, only obese individuals with the A-variant (G/A, A/A) were at increased risk for BE (OR 3.11; 95%CI 1.12-8.63), while obese individuals with the G/G variant were not at increased risk for BE (OR 2.91; 95%CI 0.69-12.15). CONCLUSION: We conclude that the common IGF-IR gene polymorphism G1013A modulates the risk of obesity for EADC, an effect most likely mediated by altered the receptor function by influencing gene transcription or mRNA stability. These findings further implicate the insulin-like growth factor axis in the molecular pathogenesis of EADC, and represent a plausible mechanistic link underlying the association between obesity and malignancy.
BACKGROUND: To investigate potential biologic mechanisms underlying the association between obesity and risk for esophageal adenocarcinoma (EADC), we studied the frequency of a common polymorphism of the insulin-like growth factor I receptor (IGF-IR) gene in patients with either gastroesophageal reflux disease (GERD), premalignant Barrett esophagus (BE) and or invasive EADC. METHODS: Using a well characterized series of 431 individuals enrolled in a case-control study, we studied the frequency of the IGF-IR gene polymorphism, G1013A. RESULTS: On multivariate analysis controlling for age and gender, in comparison to asymptomatic controls, obese individuals with the polymorphic A-variant (G/A, A/A) were found to have significantly increased risk for EADC (OR 4.81; 95%CI 1.09-21.15), whereas obese individuals with the G/G variant were not at statistically significant increased risk (OR 2.69; 95%CI 0.41-17.62). Similarly, compared to asymptomatic controls, only obese individuals with the A-variant (G/A, A/A) were at increased risk for BE (OR 3.11; 95%CI 1.12-8.63), while obese individuals with the G/G variant were not at increased risk for BE (OR 2.91; 95%CI 0.69-12.15). CONCLUSION: We conclude that the common IGF-IR gene polymorphism G1013A modulates the risk of obesity for EADC, an effect most likely mediated by altered the receptor function by influencing gene transcription or mRNA stability. These findings further implicate the insulin-like growth factor axis in the molecular pathogenesis of EADC, and represent a plausible mechanistic link underlying the association between obesity and malignancy.
Authors: Katarina B Greer; Cheryl L Thompson; Lacie Brenner; Beth Bednarchik; Dawn Dawson; Joseph Willis; William M Grady; Gary W Falk; Gregory S Cooper; Li Li; Amitabh Chak Journal: Gut Date: 2011-09-19 Impact factor: 23.059
Authors: Chung-Jung Chiu; Yvette P Conley; Michael B Gorin; Gary Gensler; Chao-Qiang Lai; Fu Shang; Allen Taylor Journal: Invest Ophthalmol Vis Sci Date: 2011-11-25 Impact factor: 4.799
Authors: Shruti G Dighe; Jianhong Chen; Li Yan; Qianchuan He; Puya Gharahkhani; Lynn Onstad; David M Levine; Claire Palles; Weimin Ye; Marilie D Gammon; Prasad G Iyer; Lesley A Anderson; Geoffrey Liu; Anna H Wu; James Y Dai; Wong-Ho Chow; Harvey A Risch; Jesper Lagergren; Nicholas J Shaheen; Leslie Bernstein; Douglas A Corley; Hans Prenen; John deCaestecker; David MacDonald; Paul Moayyedi; Hugh Barr; Sharon B Love; Laura Chegwidden; Stephen Attwood; Peter Watson; Rebecca Harrison; Katja Ott; Susanne Moebus; Marino Venerito; Hauke Lang; Rupert Mayershofer; Michael Knapp; Lothar Veits; Christian Gerges; Josef Weismüller; Ines Gockel; Yogesh Vashist; Markus M Nöthen; Jakob R Izbicki; Hendrik Manner; Horst Neuhaus; Thomas Rösch; Anne C Böhmer; Arnulf H Hölscher; Mario Anders; Oliver Pech; Brigitte Schumacher; Claudia Schmidt; Thomas Schmidt; Tania Noder; Dietmar Lorenz; Michael Vieth; Andrea May; Timo Hess; Nicole Kreuser; Jessica Becker; Christian Ell; Christine B Ambrosone; Kirsten B Moysich; Stuart MacGregor; Ian Tomlinson; David C Whiteman; Janusz Jankowski; Johannes Schumacher; Thomas L Vaughan; Margaret M Madeleine; Laura J Hardie; Matthew F Buas Journal: Carcinogenesis Date: 2021-04-17 Impact factor: 4.944