Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
Ann Surg Oncol. 2013 Dec;20 Suppl 3:S492-9. doi: 10.1245/s10434-013-2869-x. Epub 2013 Jan 26.
Cyclin D1 (CCND1) is an important cell-cycle regulator involved in carcinogenesis and progression of prostate cancer. We tested whether genetic variations within the CCND1 gene are related to clinical outcomes in prostate cancer patients receiving radical prostatectomy.
A total of 320 clinical localized prostate cancer patients who underwent radical prostatectomy in Taiwan were prospectively follow-up in this study. A total of 5 tagged single-nucleotide polymorphisms that captured the genetic variability across the CCND1 gene were genotyped, and the prognostic significance on prostate-specific antigen (PSA) recurrence was assessed using the Kaplan-Meier analysis and Cox regression model.
We found a polymorphism, rs9344, and 2 haplotypes, GAGG and CTGG, consisting of rs667515, rs2450254, rs9344, and rs678653, were associated with PSA recurrence (P ≤ 0.033). After adjusting for other clinicopathologic predictors, including age, PSA levels, pathologic stage, Gleason score, and surgical margin, rs9344 and the haplotype CTGG remained significant (P ≤ 0.044). The model based on clinical variables plus CCND1 rs9344 or haplotype showed improvement over the model without genetic information, as indicated by ≥ 7.2 % net reclassification improvement (P ≤ 0.040), integrated discrimination index (P ≤ 0.041), and likelihood ratio test (P ≤ 0.028).
Our data suggest that the CCND1 rs9344 and a specific haplotype CTGG may be prognostic factors for PSA recurrence after radical prostatectomy.
细胞周期蛋白 D1（CCND1）是参与前列腺癌发生和进展的重要细胞周期调节剂。我们检测了 CCND1 基因内的遗传变异是否与接受根治性前列腺切除术的前列腺癌患者的临床结局相关。
本研究前瞻性随访了台湾 320 例接受根治性前列腺切除术的局部前列腺癌患者。共对 5 个标记单核苷酸多态性进行基因分型，这些单核苷酸多态性捕获了 CCND1 基因内的遗传变异性，并使用 Kaplan-Meier 分析和 Cox 回归模型评估其对前列腺特异性抗原（PSA）复发的预后意义。
我们发现一个多态性 rs9344 和 2 个单倍型 GAGG 和 CTGG，由 rs667515、rs2450254、rs9344 和 rs678653 组成，与 PSA 复发相关（P≤0.033）。在调整了包括年龄、PSA 水平、病理分期、Gleason 评分和手术切缘在内的其他临床病理预测因子后，rs9344 和 CTGG 单倍型仍然具有显著性（P≤0.044）。基于临床变量加 CCND1 rs9344 或单倍型的模型比没有遗传信息的模型显示出更好的效果，表现为净重新分类改善≥7.2%（P≤0.040）、综合判别指数（P≤0.041）和似然比检验（P≤0.028）。
我们的数据表明，CCND1 rs9344 和特定的 CTGG 单倍型可能是根治性前列腺切除术后 PSA 复发的预后因素。
