Carcinogenesis Advance Access published online on February 2, 2007
Carcinogenesis, doi:10.1093/carcin/bgm026
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Genetic variability in prostaglandin synthesis, fish intake, and risk of colorectal polyps
1 Fred Hutchinson Cancer Research Center, Seattle, Washington, 98109
2 Department of Epidemiology, University of Washington, Seattle, Washington, 98195
3 Departments of Internal Medicine and Biochemistry and Molecular Biology, University of Texas Health Science Center at Houston, Houston, Texas, 77030
Corresponding author and to whom requests for reprints should be made: Cornelia Ulrich, PhD, Associate Member, Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, M4-B402, Seattle, WA 98109-1024, Phone: 206-667-7617 Fax: 206-667-7850, Email: nulrich{at}fhcrc.org
Dietary polyunsaturated fatty acids (PUFAs) can be converted to prostaglandins and leukotrienes. Metabolism of omega-6 (n-6) PUFAs results in the production of pro-inflammatory mediators while downstream products of omega-3 (n-3) PUFAs have lower inflammatory activity. Elevated n-3 PUFA intake from dietary fish may be associated with lower risk of colorectal neoplasia among those with genetic variants resulting in higher levels of pro-inflammatory mediators. We investigated interactions between dietary fish intake and polymorphisms in COX-1, COX-2, ALOX5, and PGIS in a case-control study of adenomas (N=522), hyperplastic polyps (N=194) and polyp-free controls (N=626). Polyp risk did not differ by fish intake. A suggested interaction with fish intake was observed for COX-1 P17L. Among those who were homozygous wildtype, increasing fish intake was associated with a modestly reduced risk of adenoma, whereas among those with at least one variant allele, the reverse trend was observed (p-interaction=0.08). The interaction was statistically significant when NSAID use was also taken into account: among those with COX-1 17PP genotypes, high fish intake and regular NSAID use was associated with a decreased risk compared to low fish intake and low NSAID use (OR = 0.60, 95% CI 0.33-1.09). The opposite association was observed among those with COX-1 17PL or LL genotypes (p-interaction=0.04). Our results suggest that the effects of dietary n-3 PUFA intake and NSAID use may differ by genetic variation in COX-1.
Key Words: Prostaglandins • lipoxygenases • fish • fat intake • colorectal cancer • colorectal polyps • NSAIDs • aspirin
Received November 29, 2006; revised January 14, 2007; accepted January 16, 2007.