IL-6 −174G/C Polymorphism and IL-6 Serum Levels in Patients with Liver Cirrhosis and Hepatocellular Carcinoma

Abstract

Recently, a link between high levels of circulating IL-6 and hepatocellular carcinoma (HCC) has been proposed. In addition, single nucleotide polymorphisms (SNPs) in the promoter region of the IL-6 gene have been reported to be related to several inflammatory-related conditions, including cancer. The purpose of this article is: (1) to evaluate the frequencies of SNPs in the IL-6 promoter region at position -174 and IL-6 serum levels in a group of patients with HCC and underlying liver cirrhosis (LC), and compare them with a group of LC patients without HCC; (2) to determine whether a possible correlation exists between the allelic variations, IL-6 serum levels, and the risk of developing HCC. The study included 105 HCC and 95 LC patients. Genomic DNA was isolated using commercially available kits. DNA samples were typed for relevant SNPs of the IL-6 promoter region (-174 G>C, G allele being associated with higher levels of the cytokine). The Restriction Fragment Length Polymorphism (RFLP-PCR) method was used to type the SNPs. IL-6 serum levels were determined using an ultrasensitive commercially available ELISA kit. IL-6 serum levels were higher in G/G compared to C/C genotypes only in HCC (z=2; p=0.04) and G/G versus G/C (z=1.8; p<0.03). IL-6 serum levels in G carriers (G/G+G/C) were higher in HCC 4.8 (0.2-17.5) versus LC patients 2.2 (0.07-11.5) (z=2.8; p=0.004). There was no difference for genotype C/C. IL-6 serum levels in HCC correlated with G carriers (G/G+G/C) (ρ=0.25, p=0.05). A positive correlation was also found between sIL-6 levels and some parameters of liver function both in LC and in HCC patients.

The tumor microenvironment in hepatocellular carcinoma (Review)

“…Furthermore, Coskun et al showed that in breast cancer patients, higher serum levels of IL-6 could be used to distinguish primary or metastatic liver tumors from benign HCC lesions (152). Studies focusing on the association between IL-6 polymorphisms and HCC risk are still controversial, further studies are warrented to clarify these differing findings (153)(154)(155).…”

Combined Effects of Six Cytokine Gene Polymorphisms and SNP-SNP Interactions on Hepatocellular Carcinoma Risk in Southern Guangxi, China

“…IL-6 is a multifunctional cytokine that serves pro-and anti-inflammatory functions. The level of IL-6 is higher in HCC patients than in healthy individuals (Giannitrapani et al, 2011). Numerous cytokines participate in the construction of a highly complex and coordinated network in which they modulate their own synthesis and that of other cytokines (Balkwill et al, 1989;Elias et al, 1992).…”

Genetic Factors, Viral Infection, Other Factors and Liver Cancer: An Update on Current Progress

“…A case-control study conducted in Turkey (Ataseven et al, 2006) measured the IL-6 serum level among 70 subjects in total, and found that the serum level was correlated with the disease advancement. The latest epidemiological approach performed in Italy observed similar trend between IL-6 serum level and HCC, furthermore, the G carriers of -174G/C polymorphism had higher IL-6 serum level in HCC patients than that of subjects with LC (Giannitrapani et al, 2011). Polymorphisms in TNF-alpha may change the regulation of immune cells and malfunction of itself.…”