Department of Microbiology, School of Basic Medical Science, Peking University Health Science Center, Beijing, China.
DNA Cell Biol. 2012 Jun;31(6):1107-13. doi: 10.1089/dna.2011.1521. Epub 2012 Feb 3.
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.
一个常见的多态性（G870A）在 CCND1 基因的外显子 4/内含子 4 边界已经连接到一个备用的转录本，周期蛋白 D1b，其优先编码一种具有增加的转化能力的蛋白质与全长 D1a。因此，CCND1 G870A 多态性可能影响个体对某些肿瘤的易感性。在本研究中，我们调查了 CCND1 G870A 多态性与中国北方人群中神经胶质瘤发生风险的关系。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析，在 170 例神经胶质瘤患者和 170 例年龄、性别匹配的健康对照中进行了 CCND1 G870A 基因分型。CCND1 870 A 等位基因在患者中比在对照组中更频繁地观察到（0.57 对 0.48，p=0.03），并且与 GG 和 AG 基因型相比，AA 基因型的神经胶质瘤癌症风险增加（比值比[OR]=1.828；95%置信区间[CI]：1.150-2.908，p=0.01），特别是在女性组或年龄≤45 组（OR=2.204，95%CI：1.220-3.981，p=0.008）。在世界卫生组织（WHO）分级 II 级和 III 级神经胶质瘤亚组中，也观察到 AA 基因型与神经胶质瘤风险之间存在显著相关性。进一步的逆转录酶-聚合酶链反应分析（RT-PCR）也显示，在神经胶质瘤患者中，AA 基因型与更高的 cyclin D1b 表达之间存在更强的正相关，无论是在平均值还是在同一肿瘤组织中的 cyclin D1b/cyclin D1a 比值（p=0.008，p=0.004）。总之，我们的数据表明，CCND1 G870A 多态性调节神经胶质瘤组织中的致癌 cyclin D1b 表达，并且可能与中国人群中神经胶质瘤风险增加有关。
