Association between interleukin-18 variants and prostate cancer in Slovak population

Abstract

Interleukin-18 (IL-18), pro-inflammatory cytokine, plays important role in antitumor immunity. Polymorphisms in the IL-18 gene may lead to its altered production/activity and such modulate susceptibility to prostate cancer. The aim of this study was to evaluate the relationship between the -607 and +105 polymorphisms in the IL-18 gene and the risk of prostate cancer development and progression in Slovak population. The study was performed using 425 patients with prostate cancer, 270 patients with benign prostatic hyperplasia (BHP) and 263 healthy male controls. The statistically significant association of the -607 AC genotype (OR = 2.24; p < 0.001), CC genotype (OR = 1.86; p = 0.006), as well as C allele (OR = 1.27; p = 0.033) with the higher risk of prostate cancer development was observed. No association of the IL-18 -607 polymorphism and BHP was detected. The subset analysis revealed the significant association of the -607 AC genotype (OR = 2.01; p = 0.008) with development of higher-grade carcinomas (Gleason score ≥7) and the strong association of the -607 AC genotype (OR = 3.11; p < 0.001), CC genotype (OR = 2.96; p < 0.001) as well as C allele (OR = 1.51; p = 0.003) with the higher risk of prostate cancer development in the group of patients with PSA < 10 ng/ml. The -607 AC genotype was also connected with significantly higher IL-18 plasma concentrations. No association between the IL-18 +105 polymorphism and prostate cancer was observed. The analysis of the distribution of the -607 and +105 haplotypes showed significant association of the - 607 C/ + 105 A and - 607 C/ + 105 C haplotypes with the risk of prostate cancer. This study found that the IL-18 -607 promoter polymorphism could contribute to prostate cancer development in Slovak population. Its presence was also associated with development of higher-grade carcinomas and therefore may influences the prognosis and aggressiveness of the disease.

Interleukin‐18 expression in oral squamous cell carcinoma: its role in tumor cell migration and invasion, and growth of tumor cell xenografts

“…However, other studies showed that IL-18 was able to promote tumor development and progression by showing higher levels of serum IL-18 in patients with gastric cancer [13] or oral cancer [14]. Jurecekova et al [15] assessed the level of IL-18 in prostatic cancer and discovered that IL-18 expression was associated with advanced grades of tumor and inversely with tumor prognosis and invasion. Furthermore, the epithelial-mesenchymal transition (EMT) denotes the change in which epithelial cells lose their cell polarity and cell-cell adhesion capacity but gain migratory and invasive properties, similar to mesenchymal cells [16,17], and is one of the main characteristics of tumor cell migration and invasion [16,18,19].…”

Association between IL-18 -607 C/A Polymorphism and the Risk of Prostate Cancer: A Meta-Analysis of Case-Control Studies

“…There was no additional article after manual search of references cited in the published studies. Finally, 6 relative articles (Liu et al, 2007;Liu et al, 2013;Nong et al, 2013;Dwivedi et al, 2015a;Dwivedi et al, 2015b;Jurecekova et al, 2017) were obtained . The search process is shown in Figure 1.…”

“…The selected study characteristics are listed in Table 1. There were 5 case-control studies of subjects of Asian descent (Liu et al, 2007;Liu et al, 2013;Nong et al, 2013;Dwivedi et al, 2015a;Dwivedi et al, 2015b), and 1 case-control study of Caucasians (Jurecekova et al, 2017). The genotype distribution of the control group among all studies were consistent with Hardy-Weinberg equilibrium (HWE) (P >0.05).…”

Association analysis of interleukin‐18 gene promoter region polymorphisms and susceptibility to sporadic breast cancer in Chinese Han women

“…Research showed that IL‐18 can suppress antitumor immunity in a programmed death‐1 (PD‐1)‐dependent manner, PD‐1 is a co‐inhibitory receptor and one of the major checkpoints . Furthermore, the association was verified between the 2 SNPs and the susceptibility to many cancers . However, studies focus on the role of IL‐18 polymorphisms on the risk of breast cancer remain controversial.…”

“…4 Furthermore, the association was verified between the 2 SNPs and the susceptibility to many cancers. [5][6][7][8][9][10][11][12][13][14] However, studies focus on the role of IL-18 polymorphisms on the risk of breast cancer remain controversial. To the best of our knowledge, only 3 studies have estimated the impact of IL-18 polymorphisms -137G/C and/or -607A/C on breast cancer susceptibility.…”