Cyclin D1 polymorphism (G870A) and risk for esophageal adenocarcinoma
Cyclin D1 polymorphism (G870A) and risk for esophageal adenocarcinoma
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DOI：
10.1002/cncr.21229
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发表时间：
2005-08-15
期刊：
影响因子：
6.2
通讯作者：
Guernsey, DL
中科院分区：
文献类型：
--
作者：
Casson, AG;Zheng, ZY;Guernsey, DL
背景为了研究个体对胃食管反流病、Barrett食管和食管腺癌的易感性，作者研究了CCND 1常见G870 A多态性的频率，CCND 1编码细胞周期蛋白D1，一种关键的细胞周期调控蛋白。研究人群包括307例患者，这些患者入组了一项前瞻性病例对照研究，以评价胃食管反流病（n = 126例患者）、Barrett食管（n = 125例患者）和食管腺癌（n = 56例患者）的生活方式风险因素和分子改变。对照组包括95名严格无症状的患者。提取病例组和对照组的基因组DNA，采用聚合酶链反应扩增CCND 1基因第4外显子。用BsrI酶切后，用丙烯酰胺凝胶电泳鉴定野生型和常见的G870 A多态性等位基因。比较病例组和对照组的等位基因频率（G/G、G/A、A/A）。采用免疫组化法检测病例组中cyclin D1的分布。与无症状对照组相比，调整年龄和性别后，胃食管反流病患者中A/A基因型频率增加（比值比[OR]，2.83; 95%置信区间[95% CI]，1.09-7.34），Barrett食管（OR，3.69; 95% CI，1.46-9.29）和食管腺癌（OR，5.99; 95% CI，1.86-18.96）。基因型与cyclin D1过表达之间无相关性。CCND 1 A/A基因型与胃食管反流病、Barrett食管和食管腺癌的风险增加相关。这种多态性对食管腺癌进展的确定阶段的易感性的贡献表明在内镜Barrett监测计划中的潜在应用。
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% Cl, 1.46-9.29), and esophageal adenocarcinoma (OR, 5.99; 95% Cl, 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.