174 G>C Polymorphism of Interleukin 6 Gene Promoter Affects Interleukin 6 Serum Level in Patients with Colorectal Cancer

Purpose: Experimental data suggest that interleukin 6 (IL-6) plays an important role in the development and progression of metastasis from colorectal cancer (CRC), and − 174 G > C polymorphism has been identified recently in the IL - 6 gene promoter. Therefore, the aim of the present study was to investigate the significance of this type of polymorphism in patients with CRC. Experimental Design: Using enzyme immunoassay, IL-6 concentrations were measured in preoperative serum samples from 65 stage I-IV CRC patients. DNA was extracted from peripheral blood mononuclear cells, and − 174 G > C polymorphism detected using PCR, followed by Nla III restriction enzyme digestion and electrophoresis. Results: The median IL-6 serum level was 0.14 pg/ml in patients with stage I-III disease versus 0.41 pg/ml in patients with stage IV disease ( P < 0.001). DNA amplification was possible in 62 cases. On grouping genotypes at the − 174 G > C locus as C+ ( CC and CG ) and C− ( GG ), a significant association was observed between the type of polymorphism and IL-6 serum level: the median value for IL-6 was 0.14 pg/ml in C+ patients ( n = 32) and 0.32 pg/ml in C− patients ( n = 30; P = 0.034). Moreover, in patients with hepatic metastasis the median level of IL-6 was 0.23 pg/ml in C+ patients ( n = 9) and 0.96 pg/ml in C− patients ( n = 9; P = 0.004). Conclusions: In patients with CRC, the − 174 G > C polymorphism status of the IL - 6 gene promoter affects the IL-6 serum level, particularly in the presence of hepatic metastasis.