Genetic polymorphism of CCND1 G870A and esophageal cancer susceptibility: A meta-analysis

Abstract

Abstract. The association between the polymorphism of cyclin D1 (CCND1) and esophageal carcinogenicity has been widely examined, however, it remains controversial. To evaluate the importance of CCND1 G870A polymorphism with regard to the risk of esophageal cancer, a meta-analysis was carried out that reviewed the available literature in order to clarify the controversies. This meta-analysis included 1,154 cases and 1,678 controls for CCND1 G870A polymorphism from seven published case-control studies. The odds ratio (OR) and 95% confidence interval (CI) were calculated using the Stata software version 11.1. The results were pooled using a dominant model to appropriately reflect a biological model of the genetic effect. No significant association was observed in the Caucasian (OR=1.64; 95% CI, 0.84-3.20) or the Asian populations (OR=1.30; 95% CI, 0.65-2.62), while no significant association was found in esophageal squamous cell carcinoma (ESCC) (OR=1.74; 95% CI, 0.79-3.81) or esophageal adenocarcinoma (EADC) (OR=1.18; 95% CI, 0.77-1.81). However, the comparison of A vs. G in CCND1 G870A showed significant differential susceptibility to esophageal cancer (OR=1.26; 95% CI, 1.00-1.59). These findings suggested that the CCND1 G870A polymorphism has no association with esophageal cancer risk in ethnicity and histology, respectively. Further studies are required to assess these associations in greater detail. IntroductionEsophageal cancer is a global health problem that ranked eighth in terms of incidence and sixth in terms of mortality in 2002 (1). Esophageal tumors usually lead to dysphagia, pain and other symptoms and are diagnosed via a biopsy. Esophageal cancer is divided into squamous cell carcinoma and adenocarcinoma. Squamous cell carcinoma arises from the cells that line the upper part of the esophagus. Adenocarcinoma arises from glandular cells that are present at the junction of the esophagus and stomach (2). Genetic as well as environmental factors play a role in the carcinogenesis of esophageal cancer (3,4). Individual variations in cancer risk have been associated with specific polymorphisms of various genes that are present in a significant proportion of the normal population.Cyclin D1 (CCND1) is a mitogenic sensor for the cell cycle mechanism and cellular oncogene (5). High activity of cyclin D1 can lead to chemoresistance due to the dual roles of cyclin D1 in promoting cell proliferation and inhibiting drug-induced apoptosis (6). Overexpression of cyclin D1 contributes to immature cell passage through the G1-S transition, induces propagation of unrepaired DNA damage and the accumulation of genetic errors and a selective growth advantage for the altered cells (7). Cyclin D1 are important regulators of the cell cycle and apoptosis and each contains functional single nucleotide polymorphisms (SNPs) (CCND1 G870A) that are involved in the susceptibility and outcome of various human malignancies (8).Poor statistical power has been controversial for data from individually published studies. The aim of this stu...

The Determination of Genetic Markers of Age-Related Cancer Pathologies in Populations from Kazakhstan

“…One meta-analysis (Chen et al, 2012) exhibited the statistically significant association between CCND1 G870A polymorphism and a risk for cancers of the digestive tract, including esophageal cancer (Zhang et al, 2003; Cescon et al, 2009). Another meta-analysis suggested that this polymorphism has no significant association with esophageal cancer risk in the Caucasian or the Asian populations (He et al, 2013). There are no substantial data confirming the correlation of this type of polymorphism with cervical cancer.…”

“…The results of these studies obtained on different populations can be contradictory. The evidence of an association between some rare allele variant and risk of disease can be achieved by the quantitative analysis of available publications – meta-analysis (Yin et al, 2009; Gao et al, 2011; Jiang et al, 2011; Chen et al, 2012; Cui et al, 2012; Li et al, 2012; Zhang et al, 2012; He et al, 2013). …”

Effect of the CCND1 A870G polymorphism on prostate cancer risk: a meta-analysis of 3,820 cases and 3,825 controls

“…Yang et al also reported that an A870G polymorphism in CCND1 confers an increased risk for breast cancer [ 18 ]. However, He et al revealed that a CCND1 G870A polymorphism has no association with esophageal cancer risk in ethnicity and histology [ 19 ]. Although a number of studies have been performed to assess the association between the CCND1 A870G polymorphism and prostate cancer susceptibility, the conclusions have been inconsistent.…”