RGD Reference Report - Identification of functional genetic variants in cyclooxygenase-2 and their association with risk of esophageal cancer. - Rat Genome Database

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Identification of functional genetic variants in cyclooxygenase-2 and their association with risk of esophageal cancer.

Authors: Zhang, X  Miao, X  Tan, W  Ning, B  Liu, Z  Hong, Y  Song, W  Guo, Y 
Citation: Zhang X, etal., Gastroenterology. 2005 Aug;129(2):565-76.
RGD ID: 5135528
Pubmed: PMID:16083713   (View Abstract at PubMed)

BACKGROUND & AIMS: Overexpression of cyclooxygenase-2 (COX-2) is implicated in many steps of cancer development. Single nucleotide polymorphisms (SNPs) in the COX-2 promoter might contribute to differential COX-2 expression and subsequent interindividual variability in susceptibility to cancer. This study sought to identify functional SNPs in the COX-2 promoter and evaluated their effects on the risk of developing esophageal squamous cell carcinoma (ESCC). METHODS: Thirty individual DNA samples were sequenced to search for SNPs, and the function of the SNPs was examined by a set of biochemical assays. Genotypes and haplotypes were analyzed in 1026 patients and 1270 controls, and odds ratios and 95% confidence intervals (CIs) were estimated by logistic regression. RESULTS: Three SNPs, -1290A-->G, -1195G-->A, and -765G-->C, were identified; the frequencies of variant alleles were 0.04, 0.51, and 0.02, respectively. The -1195G-->A change creates a c-MYB binding site and displays a higher promoter activity. The -1195A-containing haplotypes had significantly increased luciferase expression and COX-2 messenger RNA levels in esophageal tissues compared with the -1195G-containing counterparts. A case-control analysis showed a 1.72-fold (95% CI, 1.35-2.20) and 2.24-fold (95% CI, 1.59-3.16) excess risk of developing ESCC for the -1195AA or -765CC genotype carriers compared with noncarriers. A greater risk of developing ESCC was observed for A(-1195)-C(-765)-containing haplotypes compared with G(-1195)-G(-765)-containing haplotypes, suggesting an interaction between the -1195G-->A and -765G-->C polymorphisms in the context of haplotype. CONCLUSIONS: These findings indicate that genetic variants in COX-2 may play a role in mediating susceptibility to esophageal cancer.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PTGS2HumanEsophageal Neoplasms susceptibilityIAGP DNA:SNPs: :-1195A > G and -765G > C (human)RGD 
Ptgs2RatEsophageal Neoplasms susceptibilityISOPTGS2 (Homo sapiens)DNA:SNPs: :-1195A > G and -765G > C (human)RGD 
Ptgs2MouseEsophageal Neoplasms susceptibilityISOPTGS2 (Homo sapiens)DNA:SNPs: :-1195A > G and -765G > C (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ptgs2  (prostaglandin-endoperoxide synthase 2)

Genes (Mus musculus)
Ptgs2  (prostaglandin-endoperoxide synthase 2)

Genes (Homo sapiens)
PTGS2  (prostaglandin-endoperoxide synthase 2)


Additional Information