Juliana M Franz1, Pâmela Portela2, Patricia H Salim3, Milton Berger4, Luiz Fernando Jobim5, Rafael Roesler6, Mariana Jobim3, Gilberto Schwartsmann7. 1. Graduate Program in Medical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. Electronic address: jfranz@hcpa.edu.br. 2. Graduate Program in Medical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. 3. Department of Immunology, Hospital de Clínicas, Porto Alegre, Brazil. 4. Department of Urology, Hospital de Clínicas, Porto Alegre, Brazil. 5. Department of Immunology, Hospital de Clínicas, Porto Alegre, Brazil; Department of Internal Medicine, School of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, Brazil; Graduate Program in Surgery, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. 6. Cancer and Neurobiology Laboratory, Experimental Research Center, Hospital de Clínicas (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, Brazil; Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. 7. Department of Internal Medicine, School of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, Brazil; Cancer and Neurobiology Laboratory, Experimental Research Center, Hospital de Clínicas (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, Brazil; Department of Oncology, Hospital de Clínicas, Porto Alegre, Brazil.
Abstract
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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Interleukin-8 (IL-8) is an angiogenic CXC chemokine that plays an important role in both the development and progression of several humanmalignancies 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Authors: Yuyi Wang; Li Tu; Chi Du; Xiaoxiao Xie; Yanyang Liu; Jiantao Wang; Zhixi Li; Ming Jiang; Dan Cao; Xi Yan; Feng Luo Journal: Onco Targets Ther Date: 2018-09-06 Impact factor: 4.147