Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
Cancer Res. 2010 Feb 1;70(3):1024-32. doi: 10.1158/0008-5472.CAN-09-3742. Epub 2010 Jan 26.
The migration and invasion inhibitory protein MIIP is an inhibitor of cancer cell migration and invasion that inhibits breast tumorigenesis. In this case-control study, we evaluated the MIIP single nucleotide polymorphism (SNP) rs2295283 (codon 167, A>G, K>E) from 1,524 breast cancer patients and 1,592 age-matched controls for its association with breast cancer risk. SNP analysis included a validation set of 736 cases and 760 controls. Colony formation and cell migration assays were then conducted to functionally interrogate the genotype difference. When compared with the AA genotype, the combined AG + GG genotypes (167E) were associated with a significantly lower risk of breast cancer. In the test set, the protective effects of the AG + GG genotypes were more evident among participants with a family history of cancer. Further case series analysis revealed that the GG genotype was associated with reduced breast cancer susceptibility in cases of tumor size >2 cm and late clinical stage (II + III + IV). Colony formation assays showed that MIIP 167E (the G variant) was a more potent inhibitor of colony formation but not cell migration. These results suggest MIIP K167E as a functional genetic marker of breast cancer development and prognosis.
迁移抑制蛋白 MIIP 是一种抑制癌细胞迁移和侵袭的蛋白，能够抑制乳腺癌的发生。在这项病例对照研究中，我们评估了 1524 名乳腺癌患者和 1592 名年龄匹配对照者的 MIIP 单核苷酸多态性（SNP）rs2295283（密码子 167，A>G，K>E）与乳腺癌风险的相关性。SNP 分析包括 736 例病例和 760 例对照的验证集。然后进行集落形成和细胞迁移实验，以功能研究基因型差异。与 AA 基因型相比，AG+GG 基因型（167E）与乳腺癌风险显著降低相关。在检验集中，具有癌症家族史的参与者中，AG+GG 基因型的保护作用更为明显。进一步的病例系列分析显示，GG 基因型与肿瘤大小>2cm 和晚期临床分期（II+III+IV）的乳腺癌易感性降低相关。集落形成实验表明，MIIP 167E（G 变体）是集落形成的更有效的抑制剂，但不是细胞迁移。这些结果表明 MIIP K167E 是乳腺癌发生和预后的功能性遗传标志物。
