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台湾人群中细胞周期调控基因多态性及其在尿路尿路上皮癌易感性和预后中作用的初步证据。

Preliminary evidence of polymorphisms of cell cycle regulatory genes and their roles in urinary tract urothelial cancer susceptibility and prognosis in a Taiwan population.

作者信息

Lin Ying-Chu, Hour Tzyh-Chyuan, Tsai Yu-Chieh, Huang Shu-Pin, Wu Wen-Jeng, Chen Chung-Hsin, Pu Yeong-Shiau, Chung Shiu-Dong, Huang Chao-Yuan

机构信息

School of Dentistry, Kaohsiung Medical University, Kaohsiung City, Taiwan.

Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan.

出版信息

Urol Oncol. 2017 Sep;35(9):543.e7-543.e16. doi: 10.1016/j.urolonc.2016.08.001. Epub 2017 Jun 28.

Abstract

OBJECTIVE

Our aims were to investigate the correlations between polymorphisms in the cell cycle regulatory genes (aurora kinase A [AURKA], survivin, p21, and p53) and UC risk and prognosis.

PATIENTS AND METHODS

This study recruited 185 patients with UTUC, 46 patients with bladder cancer, and 188 hospital controls. Demographic data and possible confounding factors were collected using a standardized questionnaire. Genotyping was determined by real-time polymerase chain reaction and TaqMan probe methods.

RESULTS

Compared to the UTUC group, the control group had significantly more alcohol drinkers and coffee drinkers but not cigarette smokers. Statistical analyses showed that UTUC risk correlated with AURKA rs2273535 (adjusted odds ratio = 2.51, 95% CI = 1.07-6.15) and with survivin rs9904341 (adjusted odds ratio = 1.82, 95% CI = 1.03-3.26) polymorphisms but not with p21 and p53 polymorphisms. The bladder cancer risk showed no significant correlations with the 4 polymorphisms. In both the UTUC and UC groups, disease-free survival and overall survival were significantly longer in patients with the rs1801270CC genotype compared to those with CA+AA genotypes. Poor prognosis did not correlate with polymorphisms in AURKA, survivin, and p53 genes.

CONCLUSION

These results suggest that cell cycle regulatory gene polymorphisms rs2273535 and rs9904341 may contribute to UTUC susceptibility; gene polymorphism rs1801270 may contribute to prognosis of UTUC and prognosis of UC. The p53 polymorphisms may not correlate with UTUC susceptibility and prognosis of UTUC or UC. Further well-designed, large-scale studies are needed to clarify these findings.

摘要

目的

我们的目的是研究细胞周期调控基因(极光激酶A[AURKA]、生存素、p21和p53)多态性与上尿路上皮癌(UTUC)风险及预后之间的相关性。

患者与方法

本研究招募了185例UTUC患者、46例膀胱癌患者和188例医院对照者。使用标准化问卷收集人口统计学数据及可能的混杂因素。通过实时聚合酶链反应和TaqMan探针法进行基因分型。

结果

与UTUC组相比,对照组中饮酒者和咖啡饮用者明显更多,但吸烟者并非如此。统计分析表明,UTUC风险与AURKA rs2273535(调整优势比=2.51,95%可信区间=1.07-6.15)及生存素rs9904341(调整优势比=1.82,95%可信区间=1.03-3.26)多态性相关,但与p21和p53多态性无关。膀胱癌风险与这4种多态性均无显著相关性。在UTUC组和上尿路上皮癌(UC)组中,rs1801270CC基因型患者的无病生存期和总生存期均显著长于CA+AA基因型患者。预后不良与AURKA、生存素和p53基因的多态性无关。

结论

这些结果表明,细胞周期调控基因多态性rs2273535和rs9904341可能与UTUC易感性有关;基因多态性rs1801270可能与UTUC的预后及UC的预后有关。p53多态性可能与UTUC易感性以及UTUC或UC的预后无关。需要进一步设计良好的大规模研究来阐明这些发现。

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