[Genetic variants, circulating levels of monocyte chemoattractant protein-1 with risk of breast cancer: a case-control study and Mendelian randomization analysis].

Objective: To assess the association of genetic polymorphisms and circulating levels of chemokine monocyte chemoattractant protein-1 (MCP1) with risk of breast cancer. Methods: A total of 820 patients with pathologically confirmed breast cancer and 900 age-and area-of-residence-matched healthy controls who visited the hospital for routine health screening during the same period were included in this case-control study. Mendelian randomization analysis was performed using three widely followed functional single nucleotide polymorphisms (SNPs) of the MCP1 gene rs1024611, rs2857656 and rs4586 to construct instrumental variables.Results: MCP1 rs1024611 (OR=1.26, P=0.002), rs2857656 (OR=1.23, P=0.006) and rs4586 (OR=1.23, P=0.003) were significantly associated with increased risk of breast cancer. SNP rs1024611 (β=1.194, P<0.001), rs2857656 (β=1.221, P<0.001) and rs4586 (β=1.137, P<0.001) were positively correlated with higher circulating level of MCP1. The case-control study showed that an increase of 23.7 pg/ml of circulating levels of MCP1 was associated with a 0.25-fold increased risk of breast cancer. MR analysis confirmed that the genetic predicted circulating levels of MCP1 were associated with an increased risk of breast cancer, and the risk of breast cancer increased by 0.20 times with an increase of 23.7 pg/ml in MCP1. Conclusion: Genetic variants and circulating levels of MCP1 are significantly associated with the risk of breast cancer and can be used as a biomarker for early prediction of breast cancer.目的： 分析趋化因子单核细胞趋化蛋白-1（MCP1）基因多态性、循环水平与乳腺癌的关联性。 方法： 采用病例对照研究设计，纳入820例病理学诊断为乳腺癌的患者为病例组，同期到医院进行常规健康体检的年龄和居住地与病例组匹配的900名健康者为对照组。孟德尔随机化分析采用三个广泛关注的MCP1基因功能性单核苷酸多态性（SNP）位点rs1024611、rs2857656和rs4586构建工具变量，分析趋化因子MCP1循环水平与乳腺癌的关联性。 结果： MCP1 rs1024611（OR=1.26，P=0.002）、rs2857656（OR=1.23，P=0.006）和rs4586（OR=1.23，P=0.003）与乳腺癌风险增加显著相关。SNP rs1024611（β=1.194，P<0.001）、rs2857656（β=1.221，P<0.001）和rs4586（β=1.137，P<0.001）的罕见等位基因与MCP1循环水平呈正相关。病例对照研究显示，MCP1循环水平每增加23.7 pg/ml，乳腺癌风险增加0.25倍；MR分析显示，MCP1循环水平的每增加23.7 pg/ml，乳腺癌风险增加0.20倍。 结论： MCP1基因多态性与乳腺癌风险增加显著相关，MCP1循环水平升高增加乳腺癌的发病风险，MCP1可作为乳腺癌早期预测的生物学标志物。.