Department of Biochemistry, Istanbul Faculty of Medicine, Istanbul University, Istanbul, 34093, Turkey.
Gene. 2012 Dec 10;511(1):7-11. doi: 10.1016/j.gene.2012.09.011. Epub 2012 Sep 14.
The gene variants of the chemokine and chemokine receptor genes associated with inflammation may be involved in cancer initiation and progression. The aim of this study was to explore the possible association of monocyte chemoattractant protein-1 (MCP-1) A2518G, stromal cell derived factor 1 (SDF-1) 3'A and chemokine receptors CCR2A V64I, CCR5 Δ32, CCR5 59029 and CXCR4 gene polymorphisms with the risk and clinicopathological characteristics of bladder cancer (BC) in a Turkish population. The genotyping was done by PCR and PCR-Restriction Fragment Length Polymorphism (RFLP) methods in 142 histologically confirmed BC patients and 197 controls. The SDF-1 3'AA genotype conferred significantly increased susceptibility to BC. The carriers with AA genotype or at least one A allele of CCR2 had an increased risk of developing BC. CCR5 wt/Δ32 genotype and CCR5 Δ32 allele were also observed to be involved in the susceptibility to BC. Additionally, the combination of CCR2 V64I and CCR5 Δ32 (i.e., GG-wt/Δ32) was found to be associated with BC risk. With respect to the stage of BC, the AA genotype of SDF-1 and at least one T allele of CXCR4 were significantly associated with high T stage as compared to GG genotype of SDF-1 and CC genotype of CXCR4. Furthermore, BC patients with AA genotype or at least one A allele of CCR2 had an increased risk of high grade and stage tumors as compared to those with GG genotype. Our results suggest that the genetic variants of SDF-1 3'A, CCR2A V64I and CCR5 Δ32 gene polymorphisms may modify the BC risk. Furthermore, SDF-1 3'A, CCR2A V64I and CXCR4 gene polymorphisms may contribute to the muscle invasive BC in a Turkish population.
趋化因子和趋化因子受体基因的基因变异与炎症有关，可能参与癌症的发生和发展。本研究旨在探讨单核细胞趋化蛋白-1（MCP-1）A2518G、基质细胞衍生因子 1（SDF-1）3'A 和趋化因子受体 CCR2A V64I、CCR5Δ32、CCR559029 和 CXCR4 基因多态性与土耳其人群膀胱癌（BC）的风险和临床病理特征的可能关联。通过聚合酶链反应（PCR）和聚合酶链反应-限制性片段长度多态性（RFLP）方法，对 142 例组织学证实的 BC 患者和 197 例对照者进行基因分型。SDF-13'AA 基因型显著增加了 BC 的易感性。携带 AA 基因型或至少一个 CCR2A 等位基因 A 的个体患 BC 的风险增加。CCR5wt/Δ32 基因型和 CCR5Δ32 等位基因也与 BC 的易感性有关。此外，还发现 CCR2 V64I 和 CCR5Δ32（即 GG-wt/Δ32）的组合与 BC 风险相关。就 BC 的分期而言，与 SDF-1 的 GG 基因型和 CXCR4 的 CC 基因型相比，SDF-1 的 AA 基因型和 CXCR4 的至少一个 T 等位基因与高 T 分期显著相关。此外，与 CCR2 的 GG 基因型相比，CCR2A 的至少一个 A 等位基因的 AA 基因型的 BC 患者发生高级别和高分期肿瘤的风险增加。我们的研究结果表明，SDF-13'A、CCR2A V64I 和 CCR5Δ32 基因多态性的遗传变异可能改变 BC 的风险。此外，SDF-13'A、CCR2A V64I 和 CXCR4 基因多态性可能导致土耳其人群中肌肉浸润性 BC。
