Journal Article

Colorectal adenoma risk is modified by the interplay between polymorphisms in arachidonic acid pathway genes and fish consumption

Christine L.E. Siezen, Astrid I.M. van Leeuwen, Nicolien R. Kram, Manon E.M. Luken, Henk J. van Kranen and Ellen Kampman

in Carcinogenesis

Volume 26, issue 2, pages 449-457
Published in print February 2005 | ISSN: 0143-3334
Published online February 2005 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh336
Colorectal adenoma risk is modified by the interplay between polymorphisms in arachidonic acid pathway genes and fish consumption

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Associations between polymorphisms in genes (SNPs) involved in the arachidonic acid (AA) pathway and colorectal adenomas have been investigated in a Dutch case control study including 384 cases and 403 polyp-free controls. Twenty-one polymorphisms in seven candidate genes were studied and a potential modifying effect of fish consumption was considered. A protective effect on colorectal adenomas was found for the CT genotype of SNP H477H in PPARγ and the GC genotype of SNP V102V in COX-2 (OR 0.63, 95% CI 0.45–0.89 and OR 0.65, 95% CI 0.46–0.92, respectively) compared with the homozygous major genotypes. An increase in adenoma risk was observed for the TC genotype of SNP c.2242TC in COX-2 (OR 1.47, 95% CI 1.07–2.00) compared with the TT genotype. Analysis with estimated haplotypes confirmed these associations and revealed three additional associations with COX-2, sPLA2 and 15LOX haplotypes. Fish consumption modified the associations with COX-2 and PPARδ genotypes. For SNP c.-789CT in PPARδ the major genotype showed a decrease in adenoma risk for those in the highest tertile of fish consumption (T3), as compared with the lowest tertile (T1) (OR 0.65, 95% CI 0.41–1.02). Protective effects were also observed for SNPs V102V and c.2242TC in COX-2 and high fish intake. The interaction between fish consumption and c.2242TC was statistically significant, with an OR for the TT genotype and high fish consumption of 0.52 (95% CI 0.27–1.01) as compared with low fish intake. These results indicate that SNPs in genes involved in the AA pathway are associated with colorectal adenoma risk. Some of these associations are modified by fish consumption.

Keywords: AA, arachidonic acid; 95% CI, 95% confidence intervals; COX, cyclooxygenase; cPLA2, cytosolic PLA2; EPA, eicosapentaenoic acid; FAP, familial adenomatous polyposis; LOX, lipoxygenase; ORs, odds ratios; PPAR, peroxisome proliferator-activated receptor; PUFAs, polyunsaturated fatty acids; sPLA2, secretory PLA2; SNPs, single nucleotide polymorphisms; 3′-UTR, 3′-untranslated region

Journal Article.  6508 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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