Department of Pathology, Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey.
Pathobiology. 2013;80(3):138-45. doi: 10.1159/000341395. Epub 2013 Jan 17.
The aim of this study was to investigate a possible association between Rho-kinase (ROCK1 and ROCK2) gene polymorphisms and colorectal cancer (CRC) development.
Eighty-five patients operated due to CRC and 178 healthy controls with similar age and sex were included to this study. Genomic DNA from the patients and the healthy control cases was analyzed by a BioMark 96.96 dynamic array system. The protein expressions of ROCK1, ROCK2 and p53 were determined by immunohistochemical staining.
There were significant associations between ROCK1 (rs73963110 and rs35996865) and ROCK2 gene polymorphisms (rs2290156, rs10178332, rs35768389, rs10929732 and rs34945852) with CRC development. However, no marked associations were found between ROCK2 gene rs965665, rs2230774, rs6755196 and rs1515219 polymorphisms and the risk of developing CRC. Rho-kinase and p53 immunohistochemical stainings were markedly elevated in the tumor tissue. There were significant correlations between vascular and perineural invasions with ROCK2 or p53 protein expressions.
These results are the first to demonstrate the contribution of Rho-kinase in CRC development in patients. Our data showed that the ROCK1 and ROCK2 genes might be a risk factor for CRC development and that genetic polymorphisms in these genes may modify individual susceptibility to CRC in the Turkish population.
本研究旨在探讨 Rho 激酶(ROCK1 和 ROCK2)基因多态性与结直肠癌(CRC)发展之间的可能关联。
本研究纳入了 85 例因 CRC 接受手术的患者和 178 例年龄和性别相匹配的健康对照者。通过 BioMark 96.96 动态阵列系统分析患者和健康对照者的基因组 DNA。通过免疫组织化学染色测定 ROCK1、ROCK2 和 p53 的蛋白表达。
ROCK1(rs73963110 和 rs35996865)和 ROCK2 基因多态性(rs2290156、rs10178332、rs35768389、rs10929732 和 rs34945852)与 CRC 的发展存在显著关联。然而,ROCK2 基因 rs965665、rs2230774、rs6755196 和 rs1515219 多态性与 CRC 发病风险之间未发现明显关联。Rho-kinase 和 p53 的免疫组织化学染色在肿瘤组织中明显升高。ROCK2 或 p53 蛋白表达与血管和神经周围浸润之间存在显著相关性。
这些结果首次证明 Rho-激酶在患者 CRC 发展中的作用。我们的数据表明,ROCK1 和 ROCK2 基因可能是 CRC 发展的危险因素,这些基因的遗传多态性可能改变土耳其人群 CRC 的个体易感性。