title: Polymorphism in the nuclear factor kappa-B binding promoter region of cyclooxygenase-2 is associated with an increased risk of bladder cancer.
abstract: Cyclooxygenase-2 (COX-2) expression is mediated by constitutive nuclear factor (NF)-kappaB. The aim of this study was to investigate the association between the germline alteration of the NF-kappaB binding site of COX-2 and the risk of developing various types of human cancers. Using PCR and DNA sequence analysis, we performed a hospital-based case-control study involving various types of human cancers, namely cervical, breast, lung, and bladder cancer. The COX-2 gene was sequenced in 217 Korean individuals (122 cancer patients; 95 non-cancer patients). We identified 2 novel polymorphisms -1166 C-->G and -1186 T-->G, in the NF-kappaB binding promoter region of COX-2. A polymorphism in nucleotide 1186 was found to be associated with an increased risk of bladder cancer (P=0.038). However, in the case of the other cancers, no significant association was found between polymorphisms in the COX-2 promoter region and the risk of cancer. In conclusion, our results suggest that polymorphisms in nucleotide -1186, which is in the NF-kappaB binding promoter region of the COX-2 gene, may be associated with an increased risk of bladder cancer. Further research is needed to investigate the functional implications of the polymorphisms of the COX-2 promoter gene in human cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, 110-744, South Korea.
authors.forename: Sokbom
authors.initials: S
authors.lastname: Kang
authors.forename: Yong Beom
authors.initials: YB
authors.lastname: Kim
authors.forename: Moon-Hong
authors.initials: MH
authors.lastname: Kim
authors.forename: Kyung-Sik
authors.initials: KS
authors.lastname: Yoon
authors.forename: Jae Weon
authors.initials: JW
authors.lastname: Kim
authors.forename: Noh Hyun
authors.initials: NH
authors.lastname: Park
authors.forename: Yong Sang
authors.initials: YS
authors.lastname: Song
authors.forename: Daehee
authors.initials: D
authors.lastname: Kang
authors.forename: Keun-Young
authors.initials: KY
authors.lastname: Yoo
authors.forename: Soon Beom
authors.initials: SB
authors.lastname: Kang
authors.forename: Hyo Pyo
authors.initials: HP
authors.lastname: Lee
mesh_terms: D014408:Biomarkers, Tumor; D016022:Case-Control Studies; D051546:Cyclooxygenase 2; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D016328:NF-kappa B / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D016328:NF-kappa B; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases