-174G/C polymorphism in the interleukin-6 promoter is differently associated with prostate cancer incidence depending on race

Abstract

Interleukin-6 (IL-6), a pro-inflammatory cytokine, is involved in prostate cancer progression, including androgen independence. Serum IL-6 levels also correlate with prostate tumor burden, prostate-specific antigen levels and metastasis. Since circulating cytokine levels vary considerably inter-individually, such variation could be linked to genetic factors, including genetic polymorphism. The -174G>C/rs1800795 polymorphism in the IL-6 promoter is functionally relevant in terms of transcriptional regulation and disease association. We investigated a possible association of the -174G/C polymorphism with prostate cancer. Since significant racial disparities exist in prostate cancer incidence, we also investigated this association between the -174G/C polymorphism and prostate cancer in Caucasians and African-Americans, separately. Direct sequencing of the PCR amplicon from genomic DNA was used for genotyping rs1800795 in all subjects [age-matched controls (N = 140) and prostate cancer patients (N = 164)]. Sample size and power was calculated using the PGA software. We found the GG genotype to be associated with increased risk of prostate cancer in Caucasian subjects, whereas the CC genotype was associated with increased risk in the African-American sample set. Such a dimorphic genotypic association with cancer and race is unique and suggests a complex gene-gene and gene-environment interaction.

Role of interleukin-6 gene polymorphisms in the development of prostate cancer

“…The authors of several previous studies have reported an association between IL-6 gene polymorphisms and prostate cancer risk, but the results are inconsistent (Bao et al, 2008;Magalhães et al, 2013;Mandić et al, 2013;Mandal et al, 2014;Yang et al, 2014). Mandal et al (2014) conducted a study in Caucasian subjects and found that the GG genotype of IL-6-174G>C was associated with increased risk of prostate cancer.…”

“…Mandal et al (2014) conducted a study in Caucasian subjects and found that the GG genotype of IL-6-174G>C was associated with increased risk of prostate cancer. Mandić et al (2013) reported that IL-6-174G>C gene polymorphisms influence susceptibility to prostate cancer.…”

“…Therefore, this cytokine could contribute to the initiation, development, and metastasis of prostate cancer. Several studies have shown an association between IL-6 gene polymorphisms and the risk of prostate cancer, but the results are inconclusive (Magalhães et al, 2013;Mandić et al, 2013;Mandal et al, 2014;Yang et al, 2014). In this study, we investigated the role of two functional polymorphisms, IL-6-174G>C (rs1800795) and IL-6-572C>G (rs1800796), in the development of prostate cancer.…”

Association of interleukin-6 (-174 G/C) polymorphism with the prostate cancer risk: A meta-analysis

“…With regards to prostate cancer, the Mandić et al (30) study indicated that the IL-6 -174 single-nucleotide polymorphism (SNP) distribution may vary between ethnicities and that a single cytokine-gene polymorphism probably has only a minor influence on prostate cancer susceptibility. The study by Pierce et al (31) suggested that circulating IL-6 and its gene polymorphism did not influence the prostate cancer risk, whereas Mandal et al (32) had an opposing opinion. Due to these conflicting results, the present meta-analysis was conducted to provide a comprehensive assessment of the associations of the IL-6 (-174 G/C) gene polymorphism with the risk of prostate cancer.…”

Genes de patogenicidade de Helicobacter pylori, polimorfismos de citocinas e fatores ambientais afetam o desenvolvimento de doenças gástricas: uma visão geral

“…65 Moreover, it is involved in the regulation of various cellular functions, such as, proliferation, apoptosis and angiogenesis. 66 A nucleotide change from G to C at position -174 in the promoter region of the IL-6 genewas described. This SNP may result in inter-individual variation in transcription and expression of the IL-6; and therefore influence an individual's susceptibility to a diverse range of diseases.…”