CYCLOOXYGENASE-2 169C>G GENE POLYMORPHISM AND PROSTAGLANDIN E2 LEVEL IN BREAST CANCER

Abstract

Aims: Cyclooxygenase 2 (COX-2) with the resulting prostaglandin E2 (PGE2) are linked to increased risk of human breast cancer (BC). The aim of this study was to determine COX-2 169C>G gene polymorphism and PGE2 level at various stages of BC clarifying the role of COX-2 gene polymorphism and PGE2 in relation to BC.
Methods: The study population comprised 80 women at different stages of BC and 30 gender- and age-matched healthy control subjects. Plasma PGE2 was measured by enzyme-linked immunosorbent assay, the COX-2 gene polymorphism at position 169C>G was determined using PCR–RFLP method.
Results: The mutated allele COX-2 169G frequency was 46.9% in BC patients and 28.3 % in controls; it was significantly associated with an increased risk of BC (OR: 2.65, 95 % CI: 1.31-5.42; P = 0.003). The homozygous mutant genotype (GG) significantly increased the risk of BC (OR: 7.13, 95% CI: 1.48-46.8; P = 0.004). However, COX-2 gene (GG genotype) was not associated with breast cancer stage. Plasma PGE2 levels were significantly increased in patients compared to the controls. In primary and metastatic BC, there was a significant increase in the plasma PGE2 levels towards the presence of homozygous GG compared with homozygous CC (P< 0.001).
Conclusion: The 169C>G polymorphism of the COX-2 gene was associated with the risk of BC in Egyptian women. Furthermore, individuals with COX-2 GG genotype showed significant increase in plasma PGE2 levels. PGE2 levels may serve as a predictor of poor prognosis in patients with BC.
Key words: Plasma- PGE2, Cyclooxygenase-2 gene, Polymorphism, Breast cancer.