Department of Molecular Medicine, Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
Anticancer Res. 2010 Jul;30(7):2875-80.
Cyclin D1, encoded by the gene CCND1, is a regulatory protein in the cell cycle transition from G(1) phase to S phase. A common polymorphism (A870G) at codon 242 affects splicing of the CCND1 transcript and may cause uncontrollable cellular growth. The present study was performed to test the association between A870G polymorphisms in the CCND1 gene and colorectal cancer risk and progression.
The 870 A>G polymorphism in the cyclin D1 gene was genotyped in a Turkish colorectal cancer case-control population including fifty-seven cases (35 male, 22 female; mean age + or - SD: 59.33 + or - 13.7 years) and 117 controls (63 male, 54 female; mean age + or - SD: 54.4 + or - 12.2 years) using polymerase chain reaction-restriction fragment length polymorphism analysis.
Genotype frequencies of our patients and controls both confirmed to the Hardy-Weinberg equilibrium. There was no difference in the distribution of CCND1 genotypes and frequencies of the alleles A (59.6% versus 49.6%) and G (40.4% versus 50.4%) in the colorectal cancer patients and controls, respectively. Women homozygous for the cyclin D1 870 GG genotype showed an increased risk for developing colorectal cancer compared to those with the AG+AA genotypes and this result was statistically significant (OR 5.568, 95% CI 1.270-24.417, p=0.02). On the other hand, the cyclin D1 GA genotype was associated with distant metastasis (p=0.016).
Our findings suggest that genetic variants of A870G might be associated with distant metastasis and also gender.
细胞周期蛋白 D1（Cyclin D1）由 CCND1 基因编码，是细胞周期从 G1 期向 S 期过渡的调节蛋白。位于密码子 242 处的常见多态性（A870G）影响 CCND1 转录本的剪接，可能导致细胞失控生长。本研究旨在检验 CCND1 基因中 A870G 多态性与结直肠癌风险和进展的相关性。
采用聚合酶链反应-限制性片段长度多态性分析方法，对一个土耳其结直肠癌病例对照人群（包括 57 例病例[35 例男性，22 例女性；平均年龄+或-标准差：59.33+或-13.7 岁]和 117 例对照[63 例男性，54 例女性；平均年龄+或-标准差：54.4+或-12.2 岁]）中的 cyclin D1 基因 870A>G 多态性进行基因分型。
患者和对照组的基因型频率均符合 Hardy-Weinberg 平衡。病例组和对照组的 CCND1 基因型分布和等位基因 A（59.6%比 49.6%）和 G（40.4%比 50.4%）的频率均无差异。与携带 AG+AA 基因型的女性相比，纯合 cyclin D1 870 GG 基因型的女性发生结直肠癌的风险增加，且该结果具有统计学意义（OR 5.568，95%CI 1.270-24.417，p=0.02）。另一方面，cyclin D1 GA 基因型与远处转移相关（p=0.016）。
我们的研究结果表明，A870G 多态性可能与远处转移和性别有关。
