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

Department of Oncological and Surgical Sciences, University of Padova, Padova 35128 [C. B., E. M., R. S., A. A., D. N., M. L.]; Italian National Research Center on Aging, Ancona [F. O., S. G., C. F.]; and Department of Experimental Pathology, University of Bologna, Bologna [M. B., C. F.], Italy

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 NlaIII 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.

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