环氧化酶2基因多态性与上尿路尿路上皮癌的显著相关性。

Significant Association of Cyclo-oxygenase 2 Genotypes with Upper Tract Urothelial Cancer.

作者信息

Chang Wen-Shin, Liao Cheng-Hsi, Hsu Chin-Mu, Huang Chung-Yu, Fang Hsin-Yuan, Kao Pei-Yu, Tsai Chia-Wen, Wu Hsi-Chin, Hu Pei-Shin, Wang Tzu-Chia, Syu Yun-Ru, Shui Hao-Ai, Bau Da-Tian

机构信息

Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C. Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C.

Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C. Department of Urology, Taichung Armed Forces General Hospital, Taichung, Taiwan, R.O.C.

出版信息

Anticancer Res. 2015 May;35(5):2725-30.

PMID:25964551

Abstract

AIM

Reliable biomarkers are in urgent need for diagnosis, outcome prediction and treatment-effect monitoring for upper tract urothelial carcinomas (UTUC). Although up-regulation of cyclo-oxygenase 2 (COX2) is found in stroma and tumor cells in more than half of the patients with UTUC investigated, the genomic contribution of COX2 to UTUC has not been studied. The study aimed to evaluate the association of six polymorphic genotypes of COX2 with UTUC within a Taiwanese population.

MATERIALS AND METHODS

A total of 218 patients with UTUC and 580 healthy controls were genotyped for six COX2 polymorphisms, namely A-1195G, G-765C, T+8473C, intron 1, intron 5 and intron 6, and examined for their association with UTUC risk.

RESULTS

The distribution of genotypes of COX2 G-765C and intron 5 were significantly different between patient and control groups (p=0.0001 and 0.0016, respectively), while others were not (p>0.05). The haplotype analysis showed that compared to the GG/TT haplotype of COX2 G-765C/intron 5, those carrying GG/AT variants have a significantly increased risk of UTUC (odds ratio=4.83, 95% confidence interval=1.79-13.06), while those carrying CG/TT variants have a decreased risk (odds ratio=0.26, 95% confidence interval=0.14-0.49).

CONCLUSION

Our results suggest that individual and combined COX2 G-765C/intron 5 genotypes play a role in controlling COX2 expression and UTUC development.

摘要

目的

上尿路尿路上皮癌（UTUC）的诊断、预后预测及治疗效果监测急需可靠的生物标志物。尽管在超过半数接受研究的UTUC患者的基质和肿瘤细胞中发现了环氧化酶2（COX2）上调，但COX2对UTUC的基因组作用尚未得到研究。本研究旨在评估台湾人群中COX2六种多态性基因型与UTUC的关联。

材料与方法

对218例UTUC患者和580例健康对照进行COX2六种多态性基因分型，即A-1195G、G-765C、T+8473C、内含子1、内含子5和内含子6，并检测它们与UTUC风险的关联。

结果

患者组和对照组之间COX2 G-765C和内含子5的基因型分布存在显著差异（分别为p=0.0001和0.0016），而其他基因分型无显著差异（p>0.05）。单倍型分析显示，与COX2 G-765C/内含子5的GG/TT单倍型相比，携带GG/AT变异的个体患UTUC的风险显著增加（优势比=4.83，95%置信区间=1.79-13.06），而携带CG/TT变异的个体风险降低（优势比=0.26，95%置信区间=0.14-0.49）。