Division of Gastroenterology, Department of Internal Medicine, Kaoshiung Armed Forces General Hospital, Kaoshiung, Taiwan, R.O.C. Division of Gastroenterology, Department of Internal Medicine, Taichung Armed Forces General Hospital, Taichung, Taiwan, R.O.C. Department of Medicine, National Defense Medical Center, Taipei, Taiwan, R.O.C.
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, R.O.C. Department of Pharmacy, Taichung Armed Forces General Hospital, Taichung, Taiwan, R.O.C.
Anticancer Res. 2014 Sep;34(9):4963-8.
Gastric cancer is one of the most common malignant tumors worldwide. Due to the complex initiation and intricate progression mechanisms, early detection and effective treatment of gastric cancer are both difficult to achieve. The genetic polymorphisms encoding critical protein cyclin D1 (CCND1) to regulate cell cycle transition from G1 phase to S phase may determine the susceptibility of individuals to gastric cancer. The study aimed to examine the contribution of CCND1 genotypes to gastric cancer risk in Taiwan.
The genotypes of CCND1 A870G (rs9344) and G1722C (rs678653) were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis among 358 gastric patients and 358 cancer-free controls, and the distribution of genotypic and allelic frequencies among the two groups were compared.
The results showed that there were significant differences between gastric cancer and control groups in the distribution of the genotypes (p=6.86×10(-4)) and allelic frequency (p=0.0016) in the CCND1 A870G genotype. In addition, individuals who carried the AG or GG genotype had 0.55- and 0.51-fold of odds ratios of developing gastric cancer compared to those who carried the AA genotype (95% confidence intervals [CI]=0.39-0.76 and 0.32-0.81, respectively). There was no such association of CCND1 G1722C with gastric cancer. Furthermore, there was an obvious interaction of the CCND1 A870G genotype with personal smoking habit on gastric cancer risk (p=0.0005).
Cell-cycle regulation may play a role in gastric cancer initiation and development and the CCND1 A870G genotype maybe a useful biomarker for detection of early gastric cancer.
胃癌是全球最常见的恶性肿瘤之一。由于其起始和进展机制复杂，早期检测和有效治疗均较为困难。细胞周期调控蛋白 cyclin D1（CCND1）编码的关键蛋白的遗传多态性，可能决定了个体对胃癌的易感性，其能够调控细胞周期从 G1 期向 S 期的转换。本研究旨在探讨 CCND1 基因型对台湾地区人群胃癌发病风险的影响。
采用聚合酶链反应（PCR）结合限制性片段长度多态性（RFLP）分析方法，检测 358 例胃癌患者和 358 例对照者的 CCND1 A870G（rs9344）和 G1722C（rs678653）基因型，并比较两组间基因型和等位基因频率的分布差异。
结果显示，CCND1 A870G 基因型在胃癌组和对照组中的分布存在显著差异（p=6.86×10(-4)），等位基因频率也存在显著差异（p=0.0016）。与携带 AA 基因型者相比，携带 AG 或 GG 基因型者患胃癌的风险分别增加 0.55 倍和 0.51 倍（95%置信区间为 0.39-0.76 和 0.32-0.81）。而 CCND1 G1722C 基因型与胃癌无明显关联。此外，CCND1 A870G 基因型与个体吸烟习惯对胃癌发病风险存在明显的交互作用（p=0.0005）。
细胞周期调控可能在胃癌的发生和发展中起作用，CCND1 A870G 基因型可能是早期胃癌检测的有用生物标志物。
