Discussion
tumor, colorectal cancer, colorectal adenomas, colorectal polyp, polyp, colorectal polyp reduction, colorectal carcinogenesis
TUMOR, COLORECTAL CANCER, COLORECTAL POLYP
Using a panel of SNPs in genes controlling oxylipin signaling relevant to colorectal carcinogenesis and the pharmacology of aspirin and EPA, we report the association of several SNPs in genes encoding COX-1 (The association of A previous analysis of the interaction between We did not detect an interaction between the One of the We also demonstrated that homozygosity for the SNP (rs104522; G>C; Arg72Pro) in the coding region of the TP53 tumor suppressor gene was associated with colorectal polyp reduction in aspirin users in the seAFOod trial, in contrast with the group of individuals that had at least one major (G) allele, who did not demonstrate a reduction in colorectal polyp risk associated with aspirin use. At least one C allele at rs104522 has been reported to have an OR of 1.16 (1.05, 1.30) for presence of one or more colorectal adenomas compared with homozygous G:G individuals in a meta-analysis of genetic association studies of colorectal adenomas (We did not observe any gene–supplement interaction for any SNP related to the modest effect of EPA use on colorectal polyp number in the seAFOod trial. The reduction in total colorectal polyp number associated with EPA use in the seAFOod trial was modest and just failed to reach statistical significance (Strengths of this study include the comprehensive coverage of the seAFOod trial population whereby 77% of 707 seAFOod trial participants had both colonoscopy and genotype data available. We used a relatively small, custom-built SNP array of relevant genes based on In summary, we report novel gene–chemoprevention (aspirin) interactions from the seAFOod polyp prevention trial. SNPs in COX-1, COX-2, LOX isoforms, and TP53 should be further evaluated as biomarkers of aspirin chemoprevention efficacy, alone and in combination with other polymorphisms reported to predict colorectal polyp and/or colorectal cancer risk reduction by aspirin (