CCND1G870A Polymorphism with Altered Cyclin D1 Transcripts Expression Is Associated with the Risk of Glioma in a Chinese Population

Abstract

A common polymorphism (G870A) in the exon 4/intron 4 boundary of CCND1 gene has been linked to an alternate transcript, cyclin D1b, which preferentially encodes a protein with an increased transforming capability compared with the full-length D1a. Therefore, the CCND1 G870A polymorphism may influence an individual's susceptibility to the development of certain tumors. In the present study, we investigated the association of CCND1 G870A polymorphism with glioma cancer risk in a northern Chinese population. By polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, CCND1 G870A genotyping was carried out among 170 glioma patients and 170 age, gender-matched healthy control subjects. The CCND1 870 A allele was more frequently observed in patients than in controls (0.57 vs. 0.48, p=0.03), and an increased risk of glioma cancer was observed for the AA genotype compared with the GG and AG genotypes (odds ratio [OR]=1.828; 95% confidence interval [CI]: 1.150-2.908, p=0.01), particularly among female groups, or ages ≤45 groups (OR=2.204, 95% CI: 1.220-3.981, p=0.008). Significant associations were also observed between the AA genotype and glioma risk in the subgroups of World Health Organization (WHO) grade II gliomas and grade III gliomas. Further reverse transcriptase-polymerase chain reaction analysis (RT-PCR) also revealed a stronger positive correlation between the AA genotype and higher cyclin D1b expression among glioma patients either in the mean quantitative value, or the cyclin D1b/cyclin D1a ratio in the same tumor tissue (p=0.008, p=0.004, respectively). In conclusion, our data indicate that the CCND1 G870A polymorphism modulated oncogenic cyclin D1b expression in glioma tissues and may be associated with an increased risk of gliomas in Chinese population.