Genetic variation in prostaglandin E2 synthesis and signaling, prostaglandin dehydrogenase, and the risk of colorectal adenoma
Background: Prostaglandins are important inflammatory mediators; prostaglandin E2 (PGE2) is the predominant prostaglandin in colorectal neoplasia and affects colorectal carcinogenesis. Prostaglandins are metabolites of ω-6 and ω-3 polyunsaturated fatty acids; their biosynthesis is the primary target...
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| Main Authors: | , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
February 07 2010
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| In: |
Cancer epidemiology, biomarkers & prevention
Year: 2010, Volume: 19, Issue: 2, Pages: 547-557 |
| ISSN: | 1538-7755 |
| DOI: | 10.1158/1055-9965.EPI-09-0869 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1158/1055-9965.EPI-09-0869
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| Author Notes: | Elizabeth M. Poole, Li Hsu, Liren Xiao, Richard J. Kulmacz, Christopher S. Carlson, Peter S. Rabinovitch, Karen W. Makar, John D. Potter, and Cornelia M. Ulrich |
| Summary: | Background: Prostaglandins are important inflammatory mediators; prostaglandin E2 (PGE2) is the predominant prostaglandin in colorectal neoplasia and affects colorectal carcinogenesis. Prostaglandins are metabolites of ω-6 and ω-3 polyunsaturated fatty acids; their biosynthesis is the primary target of nonsteroidal anti-inflammatory drugs (NSAID), which reduce colorectal neoplasia risk.Methods: We investigated candidate and tagSNPs in PGE2 synthase (PGES), PGE2 receptors (EP2 and EP4), and prostaglandin dehydrogenase (PGDH) in a case-control study of adenomas (n = 483) versus polyp-free controls (n = 582) and examined interactions with NSAID use or fish intake, a source of ω-3 fatty acids.Results: A 30% adenoma risk reduction was observed for EP2 4950G>A (intron 1; ORGA/AA vs. GG, 0.71; 95% confidence interval, 0.52-0.99). For the candidate polymorphism EP4 Val294Ile, increasing fish intake was associated with increased adenoma risk among those with variant genotypes, but not among those with the Val/Val genotype (Pinteraction = 0.02). An interaction with fish intake was also observed for PGES −664A>T (5′ untranslated region; Pinteraction = 0.01). Decreased risk with increasing fish intake was only seen among those with the AT or TT genotypes (OR>2 t/wk vs. <1 t/wk, 0.56; 95% confidence interval, 0.28-1.13). We also detected interactions between NSAIDs and EP2 9814C>A (intron 1) and PGDH 343C>A (intron 1). However, none of the observed associations was statistically significant after adjustment for multiple testing. We investigated potential gene-gene interactions using the Chatterjee 1 degree of freedom Tukey test and logic regression; neither method detected significant interactions.Conclusions: These data provide little support for associations between adenoma risk and genetic variability related to PGE2, yet suggest gene-environment interactions with anti-inflammatory exposures. |
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| Item Description: | Gesehen am 05.05.2023 |
| Physical Description: | Online Resource |
| ISSN: | 1538-7755 |
| DOI: | 10.1158/1055-9965.EPI-09-0869 |