Department of Obstetrics and Gynecology, Yeditepe University Hospital, Istanbul, Turkey.
In Vivo. 2010 Mar-Apr;24(2):243-8.
Chemokines and their receptors play diverse roles in malignant tumor progression, particularly as key mediators of tumor stroma interactions. C-C motif chemokine ligand 2 (CCL2) also called monocyte chemoattractant protein-1 (MCP-1), belongs to the C-C motif chemokine sub-family and is currently believed to mediate its actions through one receptor, C-C motif chemokine receptor 2 (CCR2). CCL2 has been identified as a major chemokine inducing the recruitment of macrophages in human tumors, including those of the bladder, cervix, ovary, lung and breast. In this study of Turkish women, the association of CCL2 A2518G and CCR2 V64I polymorphisms with endometrial cancer was investigated using 50 endometrial cancer patients and 211 controls. In our study, individuals with CCL2 A2518G GG genotype showed a 6.7-fold increased risk for endometrial cancer (p<0.0001) and individuals with CCL2 A2518G A allele had a 7.14-fold lower risk of endometrium cancer (p<0.0001). Individuals carrying the CCR2 64I/64I genotype had a 4.13-fold increased risk for endometrial cancer (p<0.0001). We also found that individuals carrying the CCR2 wt allele had a 4.16-fold lower risk for endometrial cancer (p=0.005). We observed that the CCL2 G: CCR2 64I haplotype frequency was significantly higher in patients compared to controls (p=0.019). In conclusion, we state that there appears to be an association between polymorphism of CCL2 and its receptor CCR2 and endometrial cancer. To the best of our knowledge, this is the first study to show such an association.
趋化因子及其受体在恶性肿瘤的进展中发挥着多样化的作用，尤其是作为肿瘤基质相互作用的关键介质。C-C 基序趋化因子配体 2（CCL2）也被称为单核细胞趋化蛋白-1（MCP-1），属于 C-C 基序趋化因子亚家族，目前被认为通过一个受体，即 C-C 基序趋化因子受体 2（CCR2）来发挥其作用。CCL2 已被确定为一种主要的趋化因子，可诱导人类肿瘤（包括膀胱癌、宫颈癌、卵巢癌、肺癌和乳腺癌）中巨噬细胞的募集。在这项针对土耳其女性的研究中，使用 50 名子宫内膜癌患者和 211 名对照者研究了 CCL2 A2518G 和 CCR2 V64I 多态性与子宫内膜癌的关系。在我们的研究中，CCL2 A2518G GG 基因型个体患子宫内膜癌的风险增加了 6.7 倍（p<0.0001），CCL2 A2518G A 等位基因个体患子宫内膜癌的风险降低了 7.14 倍（p<0.0001）。携带 CCR2 64I/64I 基因型的个体患子宫内膜癌的风险增加了 4.13 倍（p<0.0001）。我们还发现，携带 CCR2wt 等位基因的个体患子宫内膜癌的风险降低了 4.16 倍（p=0.005）。我们观察到 CCL2 G:CCR2 64I 单倍型频率在患者中明显高于对照组（p=0.019）。总之，我们认为 CCL2 和其受体 CCR2 的多态性与子宫内膜癌之间似乎存在关联。据我们所知，这是首次显示这种关联的研究。
