Polymorphism in the nuclear factor kappa-B binding promoter region of cyclooxygenase-2 is associated with an increased risk of bladder cancer.
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.
Kang
Sokbom
S
Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, 110-744, South Korea.
Kim
Yong Beom
YB
Kim
Moon-Hong
MH
Yoon
Kyung-Sik
KS
Kim
Jae Weon
JW
Park
Noh Hyun
NH
Song
Yong Sang
YS
Kang
Daehee
D
Yoo
Keun-Young
KY
Kang
Soon Beom
SB
Lee
Hyo Pyo
HP
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*
D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D016328:NF-kappa B; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases