Oliveira Indhira D, Petrilli Antonio S, Tavela Marli H, Zago Marco A, de Toledo Silvia Regina Caminada
Pediatrics Department, Pediatric Oncology Institute, Discipline of Genetic, Federal University of São Paulo, Brazil.
J Pediatr Hematol Oncol. 2007 May;29(5):293-7. doi: 10.1097/MPH.0b013e3180587e69.
The inflammatory microenvironment of tumors is characterized by the presence of cytokines and growth factor's network both in the supporting stroma and in tumor areas. These molecules may contribute to tumoral growth and progression, facilitating metastatic process. Therefore, cancer susceptibility and severity may be associated with the functional polymorphisms of inflammatory genes. We hypothesized that inflammatory gene polymorphisms may have important role for osteosarcoma patients. We studied -308G>A TNF-alpha, +252A>G TNF-beta, -174G>C IL-6, -1082A>G IL-10, +125C>G PECAM-1, and the -463A>G MPO inflammatory gene polymorphisms in 80 osteosarcoma patients and 160 control individuals using polymerase chain reaction-restriction-fragment length polymorphism method. We found that the patients with variant genotype (GG) of the +252A>G TNF-beta gene showed an event-free survival rate of 20% at 100 months. We suggest that the presence of the variant genotype (GG) of the +252A>G TNF-beta polymorphism, which leads to higher level of cytokine production, could be a facilitator mechanism in tumor progression leading to a poor event-free survival.
肿瘤的炎性微环境的特征是在支持性基质和肿瘤区域均存在细胞因子和生长因子网络。这些分子可能有助于肿瘤的生长和进展，促进转移过程。因此，癌症易感性和严重程度可能与炎性基因的功能多态性有关。我们假设炎性基因多态性可能对骨肉瘤患者具有重要作用。我们使用聚合酶链反应-限制性片段长度多态性方法，研究了80例骨肉瘤患者和160例对照个体中的-308G>A肿瘤坏死因子-α、+252A>G肿瘤坏死因子-β、-174G>C白细胞介素-6、-1082A>G白细胞介素-10、+125C>G血小板内皮细胞黏附分子-1以及-463A>G髓过氧化物酶炎性基因多态性。我们发现，+252A>G肿瘤坏死因子-β基因变异基因型（GG）的患者在100个月时的无事件生存率为20%。我们认为，+252A>G肿瘤坏死因子-β多态性的变异基因型（GG）的存在会导致细胞因子产生水平升高，这可能是肿瘤进展中导致无事件生存不良的一种促进机制。
