Rho-kinase gene polymorphism, rho-kinase and p53 protein expression in colorectal cancer patient and association with prognostic factors

Colorectal cancer (CRC) is an important global health problem. Cancer is the second cause of death in Turkey, and CRC incidence is approximately 7 per 100,000, with approximately 5,000 new cases and 3,200 deaths annually. Rho-kinases are serine/threonine kinases, and have 2 isoforms; ROCK1 and ROCK2. Rho-kinase is involved in a large number of cellular functions implicated in tumor formation, including adhesion, migration, proliferation, and apoptosis. However, the exact role that Rho-kinase plays in colorectal cancer cells remains to be elucidated. The aim of this study was to investigate a possible association between Rho-kinase gene polymorphisms, protein expressions and prognostic parameters in CRC patients in a Turkish population. P53 protein expression and correlation with prognostic parameters in CRC patients was also evaluated in this study. Eighty five patients operated due to CRC and 178 healthy controls with similar age and sex were included to this study. Polymorphisms were analyzed in genomic DNA using a BioMark 96.96 dynamic array system. The protein expressions of ROCK1, ROCK2 and p53 were determined by the immunohistochemical staining. There were significant association between ROCK1 (rs73963110, rs35996865) and ROCK2 gene (rs2290156, rs10178332, rs35768389, rs10929732, rs34945852) polymorphisms with CRC development. However, no marked associations were found between ROCK2 gene rs965665, rs2230774 (Thr431Asn), rs6755196, and rs1515219 polymorphisms and CRC. ROCK1 and ROCK2 immunohistochemical staining were markedly elevated in the tumor tissue suggesting that there was a marked increase in Rho-kinase protein expression in CRC. It has been found that there were significant correlations between vascular and perineural invasions with ROCK2 and p53 protein expressions. These results are the first to demonstrate the contribution of Rho-kinase in CRC development. Our data showed that the ROCK1 and ROCK2 gene might be a risk factor for CRC, and suggested that genetic polymorphisms in the these genes modify individual susceptibility to CRC in the Turkish population.Key words: Rho-kinase, polymorphism, protein expression, invasion, colorectal cancer