Skip to Main Content

An official website of the United States government

Government Funding Lapse

Because of a lapse in government funding, the information on this website may not be up to date, transactions submitted via the website may not be processed, and the agency may not be able to respond to inquiries until appropriations are enacted. The NIH Clinical Center (the research hospital of NIH) is open. For more details about its operating status, please visit  cc.nih.gov. Updates regarding government operating status and resumption of normal operations can be found at OPM.gov.

About this Publication
Title
Allellic variants in regulatory regions of cyclooxygenase-2: association with advanced colorectal adenoma.
Pubmed ID
16205694 (View this publication on the PubMed website)
Publication
Br. J. Cancer. 2005 Oct; Volume 93 (Issue 8): Pages 953-9
Authors
Ali IU, Luke BT, Dean M, Greenwald P
Affiliations
  • Division for Cancer Prevention, National Cancer Institute, 6130 Executive Blvd., Bethesda, MD 20892, USA. alii@mail.nih.gov
Abstract

Cyclooxygenase 2 (Cox-2) is upregulated in colorectal adenomas and carcinomas. Polymorphisms in the Cox-2 gene may influence its function and/or its expression and may modify the protective effect of nonsteroidal anti-inflammatory drugs (NSAIDs), thereby impacting individuals' risk of developing colorectal cancer and response to prevention/intervention strategies. In a nested case-control study, four polymorphisms in the Cox-2 gene (two in the promoter, -663 insertion/deletion, GT/(GT) and -798 A/G; one in intron 5-5229, T/G; one in 3'untranslated region (UTR)-8494, T/C) were genotyped in 726 cases of colorectal adenomas and 729 age- and gender-matched controls in the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial. There was no significant association between the Cox-2 polymorphisms and adenoma development in the overall population. However, in males, the relatively rare heterozygous genotype GT/(GT) at -663 in the promoter and the variant homozygous genotype G/G at intron 5-5229 appeared to have inverse associations (odds ratio (OR)=0.59, confidence interval (CI): 0.34-1.02 and OR=0.48, CI: 0.24-0.99, respectively), whereas the heterozygous genotype T/C at 3'UTR-8494 had a positive association (OR=1.31, CI: 1.01-1.71) with adenoma development. Furthermore, the haplotype carrying the risk-conferring 3'UTR-8494 variant was associated with a 35% increase in the odds for adenoma incidence in males (OR=1.35, CI: 1.07-1.70), but the one with a risk allele at 3'UTR-8494 and a protective allele at intron 5-5229 had no effect on adenoma development (OR=0.85, CI: 0.66-1.09). Gender-related differences in adenoma risk were also noted with tobacco usage and protective effects of NSAIDs. Our analysis underscores the significance of the overall allelic architecture of Cox-2 as an important determinant for risk assessment.

Related CDAS Studies
Related CDAS Projects