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Abstract

Objectives

The purpose of the current study is to assess the association between one genetic polymorphism of interleukin (IL)-6R rs2228145 and the development of cholangiocarcinoma (CCA).

Background

IL-6 is a pleiotropic cytokine synthesized by a wide range of cells and possesses proinflammatory, protective, and regenerative functions. IL-6 signals through three pathways involving membrane-bound and soluble forms of IL-6 receptor. The dysequilibrium between these pathways is implicated in numerous inflammatory disorders and malignancies, including CCA. Therapeutic blockage of these pathways has been approved for many diseases, such as rheumatoid arthritis, and its potential utility in cancer is being tested. Genetic polymorphisms, including rs2228145 which is a functional variant mimicking IL-6 therapeutic blockage, influence the balance between IL-6R signaling pathways. Thus, it impacts the disease risk. Forty-five patients with CCA, 35 patients with nonmalignant biliary disease, and 20 healthy controls were recruited. IL-6R rs2228145 was genotyped via PCR with restricted fragment length polymorphism technique.

Results

Patients with CCA demonstrated lower frequency of the CC genotype when compared to patients with nonmalignant biliary disease (P=0.038) and lower C allele frequency compared to healthy control (P=0.046). Also, CC and AC genotypes were associated with reduced levels of C-reactive protein (P=0.027 and 0.002, respectively).

Conclusion

IL-6R rs2228145 CC genotype and C allele may be related to reduced risk of CCA development. IL-6/IL-6R pathways may be implicated in the development and could be a promising therapeutic target for CCA.

Subject Area

Clinical Pathology

Article Type

Original Study

Creative Commons License

Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License
This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 4.0 International License.

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