title: Functional genetic variations of cyclooxygenase-2 and susceptibility to acute myeloid leukemia in a Chinese population.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  These findings indicate that -765G/C polymorphism in COX-2 may play a vital role in mediating individual susceptibility to AML.
authors.affiliation: 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.
authors.forename: Jian
authors.initials: J
authors.lastname: Zheng
authors.forename: Suning
authors.initials: S
authors.lastname: Chen
authors.forename: Lan
authors.initials: L
authors.lastname: Jiang
authors.forename: Yonghe
authors.initials: Y
authors.lastname: You
authors.forename: Depei
authors.initials: D
authors.lastname: Wu
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D051546:Cyclooxygenase 2 / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide
chemical_list: D051546:Cyclooxygenase 2