Abstract
BackgroundInterleukin-27 (IL-27) has been recognized as a pleiotropic cytokine with both pro- and anti-inflammatory properties. Few studies have investigated polymorphisms and serum/plasma levels of IL-27 in diseases including cancers. This study has analyzed the associations of IL-27 gene polymorphisms, as well as plasma levels of IL-27, with susceptibility to bladder cancer and clinical outcome.MethodsThree hundred and thirty-two patients (nonmuscle-invasive bladder cancer (NMIBC)/muscle-invasive bladder cancer (MIBC): 176/156) included in a 60-month follow-up program and 499 controls were enrolled. Two single nucleotide polymorphisms (SNPs), rs153109 and rs17855750, were genotyped by polymerase chain reaction (PCR) -restriction fragment length polymorphism (RFLP) method. Plasma concentration of IL-27 was determined by ELISA in 124 patients (NMIBC/MIBC: 50/74) and 151 controls.ResultsSignificantly increased risk for bladder cancer was associated with AG/GG genotypes of rs153109 (P = 0.029). No GG genotype of rs17855750 was observed in controls, while 4 patients were found to be GG homozygotes, suggesting GG genotype may be associated with bladder cancer risk (P = 0.006). For bladder cancer patients, SNP rs17855750 was also associated with increased risk for MIBC. For MIBC patients, but not NMIBC, TG/GG genotypes of rs17855750 turned out to be a protective factor for overall survival (P = 0.035). Significantly reduced plasma levels of IL-27 were observed in both NMIBC and MIBC patients compared with controls (P < 0.0001).ConclusionOur data suggest that polymorphisms and reduced plasma levels of IL-27 may predict the susceptibility to bladder cancer, and rs17855750 may be a useful marker to distinguish patients with high risk of death.
Highlights
Interleukin-27 (IL-27) has been recognized as a pleiotropic cytokine with both pro- and anti-inflammatory properties
All observed genotype frequencies in both patients and controls were in agreement with that expected under the Hardy-Weinberg equilibrium
Significant difference in genotype frequency distributions of rs153109 was observed between bladder cancer patients and controls (P = 0.029, Odds ratio (OR) = 1.37, 95 % confidence intervals (CI) = 1.03–1.82 for rs153109 in the dominant genetic model)
Summary
Interleukin-27 (IL-27) has been recognized as a pleiotropic cytokine with both pro- and anti-inflammatory properties. Few studies have investigated polymorphisms and serum/plasma levels of IL-27 in diseases including cancers. This study has analyzed the associations of IL-27 gene polymorphisms, as well as plasma levels of IL-27, with susceptibility to bladder cancer and clinical outcome. Bladder cancer is one of the most common cancers worldwide and the most frequent malignancy of the urinary tract [1]. In China, bladder cancer is the tenth most common cancer, accounting for 17,365 deaths in 2005 and mortality has steadily increased between 1991 and 2005 [2]. Clinical and epidemiologic studies have suggested that inflammation can play a direct role in cancer [6, 7]. Findings from numerous studies have suggested that inflammation is likely to have an important role [11]. Creactive protein (CRP), which is an acute-phase reactant and a useful marker of systemic inflammation, has been shown to be a biomarker for bladder cancer [12,13,14]
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