Study of the association between a MICA gene polymorphism and cholangiocarcinoma in Egyptian patients

Introduction: An inflammatory environment is the common pathway for the development of cholangiocarcinoma (CCA). The natural killer group 2D receptor (NKG2D), an activating receptor for NK cells, is a potent immune axis in the antitumor and antimicrobial immune response through its binding to NKG2D ligands (NKG2DLs). NKG2DLs are normally absent or poorly expressed in most cells; conversely, they are upregulated in stressed cells. We studied the rs2596542 polymorphism located upstream of the MICA gene, which encodes an NKG2DL, in patients with CCA as a marker for early disease detection and a possible therapeutic target. Material and methods: A case-control study was conducted on 40 patients with CCA and 45 healthy individuals (as controls). After routine examination, the rs2596542 polymorphism of the MICA gene was investigated using real-time PCR. Results: We found that a TT homozygous genotype was significantly predominant in patients with CCA (p = 0.039), with the T allele being dominantly distributed in CCA (p = 0.007). High levels of CA19-9 were significantly associated with the TT genotype in the patients. However, we did not detect significant differences in rs2596542C/T genotype and allele distribution between patients with CCA with cirrhosis and those without cirrhosis (p > 0.05). Conclusions: The MICA rs2596542 polymorphism may affect the susceptibility to CCA, but not its progression. The TT genotype could be used as a potential diagnostic marker for CCA and triggering the MICA pathway could be a promising therapeutic target.