Polymorphisms and plasma levels of IL-27: impact on genetic susceptibility and clinical outcome of bladder cancer.

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. Three 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. Significantly 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). Our 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.

白细胞介素 - 27（IL - 27）被认为是一种具有促炎和抗炎双重特性的多效性细胞因子。很少有研究对包括癌症在内的疾病中IL - 27的多态性以及血清/血浆水平进行调查。本研究分析了IL - 27基因多态性以及IL - 27血浆水平与膀胱癌易感性和临床结果的关联。 332名患者（非肌层浸润性膀胱癌（NMIBC）/肌层浸润性膀胱癌（MIBC）：176/156）参与了一项为期60个月的随访项目，同时招募了499名对照。通过聚合酶链反应（PCR） - 限制性片段长度多态性（RFLP）方法对两个单核苷酸多态性（SNP），即rs153109和rs17855750进行基因分型。通过酶联免疫吸附测定（ELISA）测定了124名患者（NMIBC/MIBC：50/74）和151名对照的IL - 27血浆浓度。 rs153109的AG/GG基因型与膀胱癌风险显著增加相关（P = 0.029）。在对照中未观察到rs17855750的GG基因型，而发现4名患者为GG纯合子，这表明GG基因型可能与膀胱癌风险相关（P = 0.006）。对于膀胱癌患者，SNP rs17855750还与MIBC风险增加相关。对于MIBC患者（而非NMIBC患者），rs17855750的TG/GG基因型是总生存期的一个保护因素（P = 0.035）。与对照相比，在NMIBC和MIBC患者中均观察到IL - 27血浆水平显著降低（P < 0.0001）。 我们的数据表明，IL - 27的多态性和血浆水平降低可能预测膀胱癌的易感性，并且rs17855750可能是区分高死亡风险患者的一个有用标志物。