Functional genetic variations of cyclooxygenase-2 and susceptibility to acute myeloid leukemia in a Chinese population.

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.