Department of Molecular and Genetic Toxicology, School of Public Health, Cancer Center of Nanjing Medical University, Nanjing, China.
DNA Cell Biol. 2010 Oct;29(10):611-7. doi: 10.1089/dna.2010.1018.
Cyclin D1 (CCND1) is a key protein in regulation of cell cycle at the G1-to-S transition phase and is essential for regulation of cell proliferation, differentiation, and transcriptional control. We hypothesized that the CCND1 G870A polymorphism is associated with risk of bladder cancer. The CCND1 G870A polymorphism was genotyped in a hospital-based case-control study of 402 bladder cancer cases and 402 control subjects using the polymerase chain reaction-restriction fragment length polymorphism method. Unconditional univariate and multivariate logistic regression analyses were used to evaluate the associations between the CCND1 G870A polymorphism and bladder cancer risk. A significantly increased risk of bladder cancer was associated with the combined variant CCND1 870GA/AA genotypes (adjusted odds ratio, 1.54; 95% confidence interval, 1.08-2.20) compared with the GG genotype, particularly among subgroups of age ≥65 years (1.74; 1.06-2.88), men (1.67; 1.15-2.44), and smokers (1.82; 1.12-2.93). Further, the G870A polymorphism was significantly associated with risk of developing superficial bladder cancer (grade 1). In addition, a meta-analysis of the G870A polymorphism and bladder cancer risk showed that the variant 870GA/AA genotypes were associated with an increased risk of bladder cancer in Asians, but not in Caucasians, which was consistent with the results of our study. The CCND1 G870A polymorphism may be a marker for the development of bladder cancer in Chinese populations. Larger studies are required to validate these findings in diverse populations.
细胞周期蛋白 D1(CCND1)是调节细胞周期 G1 期到 S 期转换阶段的关键蛋白,对于细胞增殖、分化和转录调控至关重要。我们假设 CCND1 G870A 多态性与膀胱癌风险相关。采用聚合酶链反应-限制性片段长度多态性方法,在一项基于医院的 402 例膀胱癌病例和 402 例对照的病例对照研究中,对 CCND1 G870A 多态性进行了基因分型。采用非条件单变量和多变量逻辑回归分析评估 CCND1 G870A 多态性与膀胱癌风险之间的关系。与 GG 基因型相比,CCND1 870GA/AA 基因型的联合变异型与膀胱癌风险显著增加(调整后的优势比,1.54;95%置信区间,1.08-2.20),尤其是在年龄≥65 岁(1.74;1.06-2.88)、男性(1.67;1.15-2.44)和吸烟者(1.82;1.12-2.93)亚组中。此外,G870A 多态性与浅表膀胱癌(1 级)的发病风险显著相关。此外,对 G870A 多态性与膀胱癌风险的荟萃分析表明,变异型 870GA/AA 基因型与亚洲人群膀胱癌风险增加相关,但在高加索人群中则无此相关性,这与我们的研究结果一致。CCND1 G870A 多态性可能是中国人群膀胱癌发生的标志物。需要在不同人群中进行更大规模的研究来验证这些发现。