Graduate Program in Medical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
Graduate Program in Medical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
Cytokine. 2017 Sep;97:193-200. doi: 10.1016/j.cyto.2017.06.001. Epub 2017 Jun 29.
Interleukin-8 (IL-8) is an angiogenic CXC chemokine that plays an important role in both the development and progression of several human malignancies including prostate cancer (PC). A single nucleotide polymorphism (SNP) at -251 upstream of the transcriptional start site of the IL-8 gene has been shown to influence its production. The effects of IL-8 are mediated by two highly related chemokine receptors, CXCR1 and CXCR2. The present study investigated the influence of the IL-8 and CXCR2 gene variation on susceptibility and clinicopathological characteristics of PC in a group of Brazilian subjects.
Two hundred and one patients and 185 healthy controls were enrolled in a case-control study. Blood was collected for DNA extraction; typing of IL-8 -251 T/A and CXCR2 +1208 C/T genes was performed by polymerase chain reaction with sequence-specific primers (PCR-SSP), followed by agarose gel electrophoresis. Risk association between the genotypes, PC susceptibility and tumor characteristics was estimated by odds ratio (OR) and 95% confidence intervals (95% CI) using logistic regression analysis, after adjusting for age at diagnosis.
A significant association was found between the heterozygous CXCR2 +1208 CT genotype and stage of PC. The CXCR2 +1208 CT genotype was significantly less frequent in patients with clinical stage T3-T4 compared to T1-T2 (56.7 versus 80.5%). Our findings suggest that carriers of the CXCR2 +1208 CT genotype had a protective effect for advanced PC (CT versus CC: adjusted OR=0.25; P=0.02). No association was observed between the SNP for IL-8 -251 T/A and clinicopathological parameters of PC.
These results indicated that the CXCR2 +1208 CT genotype is less frequent in advanced stages of PC, suggesting that this chemokine receptor plays a role in the pathogenesis of this disease.
白细胞介素-8（IL-8）是一种血管生成的 CXC 趋化因子，在包括前列腺癌（PC）在内的几种人类恶性肿瘤的发展和进展中起着重要作用。已经表明，转录起始位点上游 -251 处的单个核苷酸多态性（SNP）会影响其产生。IL-8 的作用是由两个高度相关的趋化因子受体 CXCR1 和 CXCR2 介导的。本研究在一组巴西受试者中调查了 IL-8 和 CXCR2 基因变异对 PC 易感性和临床病理特征的影响。
201 名患者和 185 名健康对照者参加了病例对照研究。采集血液用于 DNA 提取；通过聚合酶链反应与序列特异性引物（PCR-SSP）对 IL-8-251 T/A 和 CXCR2+1208 C/T 基因进行分型，然后进行琼脂糖凝胶电泳。使用逻辑回归分析，在调整诊断时的年龄后，通过比值比（OR）和 95%置信区间（95%CI）估计基因型、PC 易感性和肿瘤特征之间的风险关联。
发现 CXCR2+1208 CT 杂合基因型与 PC 分期之间存在显著关联。与 T1-T2 相比，临床分期 T3-T4 的患者中 CXCR2+1208 CT 基因型明显较少（56.7%比 80.5%）。我们的研究结果表明，CXCR2+1208 CT 基因型携带者对晚期 PC 具有保护作用（CT 与 CC：调整后的 OR=0.25；P=0.02）。IL-8-251 T/A 单核苷酸多态性与 PC 的临床病理参数之间没有关联。
这些结果表明，CXCR2+1208 CT 基因型在 PC 的晚期阶段较少见，提示该趋化因子受体在该疾病的发病机制中起作用。
