Cargando…

Genetic Variation in 15-Hydroxyprostaglandin Dehydrogenase and Colon Cancer Susceptibility

BACKGROUND: 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is a metabolic antagonist of COX-2, catalyzing the degradation of inflammation mediator prostaglandin E2 (PGE(2)) and other prostanoids. Recent studies have established the 15-PGDH gene as a colon cancer suppressor. METHODS: We evaluated 15...

Descripción completa

Detalles Bibliográficos
Autores principales: Thompson, Cheryl L., Fink, Stephen P., Lutterbaugh, James D., Elston, Robert C., Veigl, Martina L., Markowitz, Sanford D., Li, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3661460/
https://www.ncbi.nlm.nih.gov/pubmed/23717544
http://dx.doi.org/10.1371/journal.pone.0064122
_version_ 1782270678038216704
author Thompson, Cheryl L.
Fink, Stephen P.
Lutterbaugh, James D.
Elston, Robert C.
Veigl, Martina L.
Markowitz, Sanford D.
Li, Li
author_facet Thompson, Cheryl L.
Fink, Stephen P.
Lutterbaugh, James D.
Elston, Robert C.
Veigl, Martina L.
Markowitz, Sanford D.
Li, Li
author_sort Thompson, Cheryl L.
collection PubMed
description BACKGROUND: 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is a metabolic antagonist of COX-2, catalyzing the degradation of inflammation mediator prostaglandin E2 (PGE(2)) and other prostanoids. Recent studies have established the 15-PGDH gene as a colon cancer suppressor. METHODS: We evaluated 15-PDGH as a colon cancer susceptibility locus in a three-stage design. We first genotyped 102 single-nucleotide polymorphisms (SNPs) in the 15-PGDH gene, spanning ∼50 kb up and down-stream of the coding region, in 464 colon cancer cases and 393 population controls. We then genotyped the same SNPs, and also assayed the expression levels of 15-PGDH in colon tissues from 69 independent patients for whom colon tissue and paired germline DNA samples were available. In the final stage 3, we genotyped the 9 most promising SNPs from stages 1 and 2 in an independent sample of 525 cases and 816 controls (stage 3). RESULTS: In the first two stages, three SNPs (rs1365611, rs6844282 and rs2332897) were statistically significant (p<0.05) in combined analysis of association with risk of colon cancer and of association with 15-PGDH expression, after adjustment for multiple testing. For one additional SNP, rs2555639, the T allele showed increased cancer risk and decreased 15-PGDH expression, but just missed statistical significance (p-adjusted = 0.063). In stage 3, rs2555639 alone showed evidence of association with an odds ratio (TT compared to CC) of 1.50 (95% CI = 1.05–2.15, p = 0.026). CONCLUSIONS: Our data suggest that the rs2555639 T allele is associated with increased risk of colon cancer, and that carriers of this risk allele exhibit decreased expression of 15-PGDH in the colon.
format Online
Article
Text
id pubmed-3661460
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-36614602013-05-28 Genetic Variation in 15-Hydroxyprostaglandin Dehydrogenase and Colon Cancer Susceptibility Thompson, Cheryl L. Fink, Stephen P. Lutterbaugh, James D. Elston, Robert C. Veigl, Martina L. Markowitz, Sanford D. Li, Li PLoS One Research Article BACKGROUND: 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is a metabolic antagonist of COX-2, catalyzing the degradation of inflammation mediator prostaglandin E2 (PGE(2)) and other prostanoids. Recent studies have established the 15-PGDH gene as a colon cancer suppressor. METHODS: We evaluated 15-PDGH as a colon cancer susceptibility locus in a three-stage design. We first genotyped 102 single-nucleotide polymorphisms (SNPs) in the 15-PGDH gene, spanning ∼50 kb up and down-stream of the coding region, in 464 colon cancer cases and 393 population controls. We then genotyped the same SNPs, and also assayed the expression levels of 15-PGDH in colon tissues from 69 independent patients for whom colon tissue and paired germline DNA samples were available. In the final stage 3, we genotyped the 9 most promising SNPs from stages 1 and 2 in an independent sample of 525 cases and 816 controls (stage 3). RESULTS: In the first two stages, three SNPs (rs1365611, rs6844282 and rs2332897) were statistically significant (p<0.05) in combined analysis of association with risk of colon cancer and of association with 15-PGDH expression, after adjustment for multiple testing. For one additional SNP, rs2555639, the T allele showed increased cancer risk and decreased 15-PGDH expression, but just missed statistical significance (p-adjusted = 0.063). In stage 3, rs2555639 alone showed evidence of association with an odds ratio (TT compared to CC) of 1.50 (95% CI = 1.05–2.15, p = 0.026). CONCLUSIONS: Our data suggest that the rs2555639 T allele is associated with increased risk of colon cancer, and that carriers of this risk allele exhibit decreased expression of 15-PGDH in the colon. Public Library of Science 2013-05-22 /pmc/articles/PMC3661460/ /pubmed/23717544 http://dx.doi.org/10.1371/journal.pone.0064122 Text en © 2013 Thompson et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Thompson, Cheryl L.
Fink, Stephen P.
Lutterbaugh, James D.
Elston, Robert C.
Veigl, Martina L.
Markowitz, Sanford D.
Li, Li
Genetic Variation in 15-Hydroxyprostaglandin Dehydrogenase and Colon Cancer Susceptibility
title Genetic Variation in 15-Hydroxyprostaglandin Dehydrogenase and Colon Cancer Susceptibility
title_full Genetic Variation in 15-Hydroxyprostaglandin Dehydrogenase and Colon Cancer Susceptibility
title_fullStr Genetic Variation in 15-Hydroxyprostaglandin Dehydrogenase and Colon Cancer Susceptibility
title_full_unstemmed Genetic Variation in 15-Hydroxyprostaglandin Dehydrogenase and Colon Cancer Susceptibility
title_short Genetic Variation in 15-Hydroxyprostaglandin Dehydrogenase and Colon Cancer Susceptibility
title_sort genetic variation in 15-hydroxyprostaglandin dehydrogenase and colon cancer susceptibility
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3661460/
https://www.ncbi.nlm.nih.gov/pubmed/23717544
http://dx.doi.org/10.1371/journal.pone.0064122
work_keys_str_mv AT thompsoncheryll geneticvariationin15hydroxyprostaglandindehydrogenaseandcoloncancersusceptibility
AT finkstephenp geneticvariationin15hydroxyprostaglandindehydrogenaseandcoloncancersusceptibility
AT lutterbaughjamesd geneticvariationin15hydroxyprostaglandindehydrogenaseandcoloncancersusceptibility
AT elstonrobertc geneticvariationin15hydroxyprostaglandindehydrogenaseandcoloncancersusceptibility
AT veiglmartinal geneticvariationin15hydroxyprostaglandindehydrogenaseandcoloncancersusceptibility
AT markowitzsanfordd geneticvariationin15hydroxyprostaglandindehydrogenaseandcoloncancersusceptibility
AT lili geneticvariationin15hydroxyprostaglandindehydrogenaseandcoloncancersusceptibility