Cyclin D1 polymorphism (G870A) and risk for esophageal adenocarcinoma.
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.
Casson
Alan G
AG
Department of Surgery, Division of Thoracic Surgery, Dalhousie University, Halifax, Nova Scotia, Canada. alan.casson@dal.ca
Zheng
Zuoyu
Z
Evans
Susan C
SC
Geldenhuys
Laurette
L
van Zanten
Sander Veldhuyzen
SV
Veugelers
Paul J
PJ
Porter
Geoffrey A
GA
Guernsey
Duane L
DL
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D001471:Barrett Esophagus / Q000235:genetics / Q000378:metabolism; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism; D005764:Gastroesophageal Reflux / Q000235:genetics / Q000378:metabolism; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors
D019938:Cyclin D1