Lin Hui-Hui, Ke Hung-Lung, Hsiao Kuang-Hung, Tsai Chia-Wen, Wu Wen-Jeng, Bau Da-Tian, Chang Lin-Li
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China.
Chin J Physiol. 2011 Jun 30;54(3):196-202. doi: 10.4077/cjp.2011.amm123.
The cell cycle regulator cyclin D1 (CCND1) is thought to play a major role in the transition of cell cycle from G1 to S phase. It is known that a common CCND1 G870A genotype is associated with bladder cancer in Japan and China, but not in the Western World. There is neither a report about its role in Taiwan's population, nor its genetic role of CCND1 G870A in another worldwide urothelial cancer, upper tract urothelial cancer (UTUC). Therefore, we aimed at investigating the role of CCND1 G870A in both bladder cancer and UTUC in Taiwanese cohorts. The CCND1 G870A genotypes of 171 (101 bladder cancer and 70 UTUC) patients and 243 control subjects were determined by PCR-RFLP and their correlation with clinical and histopathological data was evaluated. The genotype analysis results showed that CCND1 GG genotype was associated with a lower risk overall in urothelial (P = 0.008, OR = 0.44, 95% CI = 0.24-0.81) and bladder cancer patients (P = 0.008, OR = 0.34, 95% CI = 0.15-0.76) than those of the AA genotype. In addition, patients carrying the AG genotype had a 0.29-fold lower odds ratio of muscle-invasive cancer procession (95% CI = 0.12-0.70) compared with those carrying the AA genotype in bladder cancer patients. Surprisingly, the GG genotype had a 5.88-fold higher odds ratio of muscle-invasive cancer procession (95% CI = 1.08-32.01) compared with those carrying the AA genotype in UTUC. No association between any CCND1 G870A genotype and higher-grade risk was found. Our results suggest that the G allele of the CCND1 G870A polymorphism may be a potential predictive and prognostic biomarker to distinguish between bladder cancer and UTUC in Taiwan.
细胞周期调节因子细胞周期蛋白D1（CCND1）被认为在细胞周期从G1期向S期的转变中起主要作用。已知常见的CCND1 G870A基因型在日本和中国与膀胱癌相关，但在西方世界并非如此。既没有关于其在台湾人群中作用的报道，也没有关于CCND1 G870A在另一种全球范围内的尿路上皮癌——上尿路尿路上皮癌（UTUC）中的遗传作用的报道。因此，我们旨在研究CCND1 G870A在台湾队列的膀胱癌和UTUC中的作用。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）确定了171例患者（101例膀胱癌和70例UTUC）和243例对照受试者的CCND1 G870A基因型，并评估了其与临床和组织病理学数据的相关性。基因型分析结果显示，与AA基因型相比，CCND1 GG基因型在尿路上皮癌患者（P = 0.008，比值比[OR] = 0.44，95%置信区间[CI] = 0.24 - 0.81）和膀胱癌患者（P = 0.008，OR = 0.34，95% CI = 0.15 - 0.76）中总体风险较低。此外，在膀胱癌患者中，携带AG基因型的患者发生肌肉浸润性癌进展的比值比相较于携带AA基因型的患者低0.29倍（95% CI = 0.12 - 0.70）。令人惊讶的是，在UTUC中，与携带AA基因型的患者相比，GG基因型发生肌肉浸润性癌进展的比值比高5.88倍（95% CI = 1.08 - 32.01）。未发现任何CCND1 G870A基因型与高级别风险之间存在关联。我们的结果表明，CCND1 G870A多态性的G等位基因可能是区分台湾地区膀胱癌和UTUC的一种潜在的预测和预后生物标志物。
