Carcinogenesis Advance Access originally published online on February 2, 2007
Carcinogenesis 2007 28(6):1259-1263; doi:10.1093/carcin/bgm026
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Genetic variability in prostaglandin synthesis, fish intake and risk of colorectal polyps
1 Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
2 Department of Epidemiology, University of Washington, Seattle, WA 98195, USA
3 Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
4 Department of Biochemistry and Molecular Biology, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
* To whom correspondence should be addressed at Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M4-B402, Seattle, WA 98109-1024, USA. Tel: +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 whereas 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 cyclooxygenase (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 wild type, 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 non-steroidal anti-inflammatory drug (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 with low fish intake and low NSAID use (odds ratio = 0.60, 95% confidence interval 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.
Abbreviations: ALOX, Lipoxygenase; CI, confidence interval; COX, Cyclooxygenase; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; NSAID, non-steroidal anti-inflammatory drug; OR, odds ratio; PUFA, polyunsaturated fatty acid
Received November 29, 2006; revised January 14, 2007; accepted January 16, 2007.