Liu Guan-Xian, Zhang Xin, Li Su, Koiiche Richard D, Sindsceii Jerry H, Song Haihan
Department of Nephrology, Huizhou Municipal Central Hospital, 41 E Ling Bei Road, Huizhou, Guangdong, 516001, China,
Tumour Biol. 2013 Oct;34(5):2741-6. doi: 10.1007/s13277-013-0827-7. Epub 2013 May 9.
Monocyte chemoattractant protein-1 (MCP-1) and its receptor CC chemokine receptor 2 (CCR2) play a major role in inflammation and proliferation of cancers. We investigated a possible association between polymorphisms in MCP-1 and CCR2 genes (MCP-1 -2518A/G and CCR2 190G/A or V64I) and the risk as well as prognosis of renal cell carcinoma (RCC). Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism in 416 RCC cases and 458 age-matched healthy controls. Frequency of MCP-1 2518GG genotype for cases and controls was 0.384 and 0.286, respectively; individuals carrying the GG genotype had a 1.89-fold increased risk of RCC than those with AA genotype (95 % confidence interval [CI] 1.24-2.81, p = 0.002; data were adjusted for age and sex). Frequency of CCR2 190AA (64I/64I) genotype for cases and controls was 0.175 and 0.076, respectively; subjects having AA genotype had a 2.68-fold increased risk of RCC compared to those with the wild-type GG genotype (95 %CI 1.71-4.17, p = 4.3 × 10(-6); data were adjusted for age and sex). When analyzing the survival rate of RCC, patients with MCP-1 -2518GG genotype revealed significantly shorter survival time compared to cases with MCP-1 -2518AA and AG genotypes (p = 0.003). Similarly, RCC cases carrying CCR2 190AA genotype showed significantly shorter survival rate than patients with GG or GA genotypes (p < 0.001). These data suggested that MCP-1 -2518A/G and CCR2 190G/A polymorphisms are new risk factors for RCC and could be used as prognostic markers for this malignancy.
单核细胞趋化蛋白-1(MCP-1)及其受体CC趋化因子受体2(CCR2)在癌症的炎症和增殖过程中起主要作用。我们研究了MCP-1和CCR2基因多态性(MCP-1 -2518A/G和CCR2 190G/A或V64I)与肾细胞癌(RCC)风险及预后之间的可能关联。通过聚合酶链反应-限制性片段长度多态性方法对416例RCC患者和458例年龄匹配的健康对照者进行基因分型。病例组和对照组中MCP-1 2518GG基因型频率分别为0.384和0.286;携带GG基因型的个体患RCC的风险是AA基因型个体的1.89倍(95%置信区间[CI] 1.24 - 2.81,p = 0.002;数据经年龄和性别校正)。病例组和对照组中CCR2 190AA(64I/64I)基因型频率分别为0.175和0.076;与野生型GG基因型个体相比,AA基因型个体患RCC的风险增加2.68倍(95%CI 1.71 - 4.17,p = 4.3×10⁻⁶;数据经年龄和性别校正)。在分析RCC患者生存率时,MCP-1 -2518GG基因型患者的生存时间显著短于MCP-1 -2518AA和AG基因型患者(p = 0.003)。同样,携带CCR2 190AA基因型的RCC患者的生存率显著低于GG或GA基因型患者(p < 0.001)。这些数据表明,MCP-1 -2518A/G和CCR2 190G/A多态性是RCC的新危险因素,可作为这种恶性肿瘤的预后标志物。