BACKGROUND: To investigate individual susceptibility to gastroesophageal reflux disease, Barrett esophagus, and esophageal adenocarcinoma, the authors studied the frequency of the common G870A polymorphism of CCND1, which encodes cyclin D1, a key cell cycle regulatory protein. METHODS: The study population included 307 patients who were enrolled in a prospective case-control study to evaluate lifestyle risk factors and molecular alterations in gastroesophageal reflux disease (n = 126 patients), Barrett esophagus (n = 125 patients), and esophageal adenocarcinoma (n = 56 patients). A control group included 95 strictly asymptomatic individuals. Genomic DNA was extracted from cases and controls, and polymerase chain reaction was used to amplify exon 4 of CCND1. After digestion with BsrI, acrylamide gel electrophoresis was used to identify the wild type and common G870A polymorphic alleles. The frequency of alleles (G/G, G/A, A/A) was compared between cases and controls. Immunohistochemistry was used to study cyclin D1 distribution in among patients in the case group. RESULTS: Compared with the asymptomatic control group, and adjusted for age and gender, increasing frequencies were seen for the A/A genotype in patients with gastroesophageal reflux disease (odds ratio [OR], 2.83; 95% confidence interval [95% CI], 1.09-7.34), Barrett esophagus (OR, 3.69; 95% CI, 1.46-9.29), and esophageal adenocarcinoma (OR, 5.99; 95% CI, 1.86-18.96). No association was seen between genotype and cyclin D1 overexpression. CONCLUSIONS: The CCND1 A/A genotype was associated with increased risk for gastroesophageal reflux disease, Barrett esophagus, and esophageal adenocarcinoma. The contribution of this polymorphism to susceptibility of defined stages of progression to esophageal adenocarcinoma suggested potential application in endoscopic Barrett surveillance programs.
BACKGROUND: To investigate individual susceptibility to gastroesophageal reflux disease, Barrett esophagus, and esophageal adenocarcinoma, the authors studied the frequency of the common G870A polymorphism of CCND1, which encodes cyclin D1, a key cell cycle regulatory protein. METHODS: The study population included 307 patients who were enrolled in a prospective case-control study to evaluate lifestyle risk factors and molecular alterations in gastroesophageal reflux disease (n = 126 patients), Barrett esophagus (n = 125 patients), and esophageal adenocarcinoma (n = 56 patients). A control group included 95 strictly asymptomatic individuals. Genomic DNA was extracted from cases and controls, and polymerase chain reaction was used to amplify exon 4 of CCND1. After digestion with BsrI, acrylamide gel electrophoresis was used to identify the wild type and common G870A polymorphic alleles. The frequency of alleles (G/G, G/A, A/A) was compared between cases and controls. Immunohistochemistry was used to study cyclin D1 distribution in among patients in the case group. RESULTS: Compared with the asymptomatic control group, and adjusted for age and gender, increasing frequencies were seen for the A/A genotype in patients with gastroesophageal reflux disease (odds ratio [OR], 2.83; 95% confidence interval [95% CI], 1.09-7.34), Barrett esophagus (OR, 3.69; 95% CI, 1.46-9.29), and esophageal adenocarcinoma (OR, 5.99; 95% CI, 1.86-18.96). No association was seen between genotype and cyclin D1 overexpression. CONCLUSIONS: The CCND1 A/A genotype was associated with increased risk for gastroesophageal reflux disease, Barrett esophagus, and esophageal adenocarcinoma. The contribution of this polymorphism to susceptibility of defined stages of progression to esophageal adenocarcinoma suggested potential application in endoscopic Barrett surveillance programs.
Authors: Vanita K Gupta; Andrew Feber; Liqiang Xi; Arjun Pennathur; Maoxin Wu; James D Luketich; Tony E Godfrey Journal: Clin Cancer Res Date: 2008-12-01 Impact factor: 12.531
Authors: Michael Lanuti; Geoffrey Liu; Jonathan M Goodwin; Rihong Zhai; Bryan C Fuchs; Kofi Asomaning; Li Su; Norman S Nishioka; Kenneth K Tanabe; David C Christiani Journal: Clin Cancer Res Date: 2008-05-15 Impact factor: 12.531
Authors: Shuo Cheng Zhang; Christie Barclay; Leigh Ann Alexander; Laurette Geldenhuys; Geoffrey A Porter; Alan G Casson; Paul R Murphy Journal: J Mol Med (Berl) Date: 2007-06-14 Impact factor: 4.599
Authors: Mohammad R Akbari; Reza Malekzadeh; Ramin Shakeri; Dariush Nasrollahzadeh; Maryam Foumani; Yulong Sun; Akram Pourshams; Alireza Sadjadi; Elham Jafari; Masoud Sotoudeh; Farin Kamangar; Paolo Boffetta; Sanford M Dawsey; Parviz Ghadirian; Steven A Narod Journal: Cancer Res Date: 2009-10-13 Impact factor: 12.701