Soochow University Laboratory of Cancer Molecular Genetics, Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, Department of Hematology, the First Affiliated Hospital of Soochow University, Suzhou, China.
Eur J Haematol. 2011 Dec;87(6):486-93. doi: 10.1111/j.1600-0609.2011.01691.x.
Cyclooxygenase-2 (COX-2) is a key enzyme involved in the synthesis of prostaglandins, which are known to play important roles in the proliferation and differentiation of leukemia cells, and inhibitors of COX-2 can suppress the proliferation and differentiation of human leukemia cell lines. Single-nucleotide polymorphisms (-765G/C: rs20417, -1195A/G: rs689466, and -1290A/G: rs689465) in the COX-2 promoter might contribute to differential COX-2 expression and subsequent interindividual variability in susceptibility to cancer.
In this case-control study, the genotypes of potential functional Single-nucleotide polymorphisms in COX-2 gene were determined with PCR-RFLP method in 446 patients and 725 controls. COX-2 mRNA level in Acute myeloid leukemia (AML) bone marrow and COX-2 protein level in serum samples were examined by real-time PCR and ELISA, respectively.
It was found that carriers with -765CC genotypes had a 2.19-fold (95% CI = 1.24-3.88; P < 0.001) excess risk of developing AML compared with non-carriers. A greater risk of developing AML was observed for A(-1195) -C(-765) haplotype compared with G(-1195) -G(-765) haplotype. Moreover, individuals with -765C-containing genotypes had significantly increased COX-2 mRNA level and protein level compared with the -765G-containing counterparts.
These findings indicate that -765G/C polymorphism in COX-2 may play a vital role in mediating individual susceptibility to AML.
环氧化酶-2（COX-2）是参与前列腺素合成的关键酶，已知前列腺素在白血病细胞的增殖和分化中发挥重要作用，COX-2 的抑制剂可以抑制人白血病细胞系的增殖和分化。COX-2 启动子中的单核苷酸多态性（-765G/C：rs20417、-1195A/G：rs689466 和 -1290A/G：rs689465）可能导致 COX-2 表达的差异，并随后导致个体对癌症易感性的差异。
在这项病例对照研究中，采用 PCR-RFLP 方法检测了 446 例患者和 725 例对照者 COX-2 基因中潜在功能单核苷酸多态性的基因型。采用实时 PCR 和 ELISA 分别检测急性髓系白血病（AML）骨髓中 COX-2mRNA 水平和血清中 COX-2 蛋白水平。
结果发现，与非携带者相比，-765CC 基因型携带者发生 AML 的风险增加了 2.19 倍（95%CI=1.24-3.88；P<0.001）。与 G(-1195)-G(-765) 单倍型相比，A(-1195)-C(-765) 单倍型发生 AML 的风险更大。此外，与携带 -765G 基因型的个体相比，携带 -765C 基因型的个体 COX-2mRNA 水平和蛋白水平显著升高。
这些发现表明 COX-2 中的-765G/C 多态性可能在介导个体对 AML 的易感性方面发挥重要作用。
