title: Cyclooxygenase-2 169C>G and 8473T>C gene polymorphisms and prostaglandin E2 level in breast cancer: a case-control study.
abstract: OBJECTIVE
  Cyclooxygenase 2 (COX-2) with the resulting prostaglandin E2 (PGE2) is linked to increased risk of human breast cancer (BC). The aim of this study was to determine COX-2 169C>G and 8473T>C gene polymorphisms 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 160 women at different stages of BC and 150 gender- and age-matched healthy control subjects. Plasma PGE2 was measured by ELISA, the COX-2 gene polymorphisms were determined using PCR-RFLP.
  
  
  RESULTS
  The variant alleles COX-2 169G and 8473C were significantly associated with BC susceptibility [OR=3.1, 95% CI (2.2-4.4), P<0.001 for 169C>G and OR=1.74, 95%CI (1.3-2.4), P=0.005 for 8473C]. However, both COX-2 gene polymorphisms were not associated with breast cancer stage. Plasma PGE2 levels were significantly increased in patients compared to the controls. In early and late stages of BC, there was a significant increase in the plasma PGE2 levels towards the presence of homozygous GG compared with homozygous CC (P<0.001) for 169 C>G, also towards the presence of CC than TT (P<0.001) for 8473T>C SNP.
  
  
  CONCLUSIONS
  The 169C>G and 8473T>C polymorphisms of the COX-2 gene were associated with the BC in Egyptian women. Furthermore, individuals with COX-2 169GG and 8473CC genotypes showed significant increase in plasma PGE2 levels. PGE2 levels may serve as a predictor of poor prognosis in patients with BC.
authors.affiliation: Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Egypt. fawzi_ms@yahoo.com
authors.forename: M S
authors.initials: MS
authors.lastname: Fawzy
authors.forename: N M M
authors.initials: NM
authors.lastname: Aly
authors.forename: S M
authors.initials: SM
authors.lastname: Shalaby
authors.forename: W H
authors.initials: WH
authors.lastname: El-Sawy
authors.forename: R S
authors.initials: RS
authors.lastname: Abdul-Maksoud
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D051546:Cyclooxygenase 2 / Q000235:genetics*; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic
chemical_list: D051546:Cyclooxygenase 2; D015232:Dinoprostone
keywords: BC; Breast cancer; COX-2; Cyclooxygenase-2 gene; ER; IHC; PCR RFLP; PCR-restriction fragment length polymorphism; PG; PR; Plasma-PGE2; Polymorphism; cyclooxygenases-2; estrogen receptors; immunohistochemical; progesterone receptors; prostaglandins