Introduction
colorectal cancer, polyp, colorectal polyp
COLORECTAL CANCER, BOWEL CANCER, COLORECTAL POLYP
A large body of evidence has accumulated from epidemiologic observations, randomized colorectal polyp prevention trials, and long-term follow-up studies of colorectal cancer outcomes after participation in vascular prevention trials, that regular aspirin use is associated with a 15% to 20% reduction in colorectal cancer risk (However, a multivariable risk prediction model utilizing these clinical features has yet to emerge that would support precision chemoprevention largely because of the dearth of an accompanying biomarker(s) of personalized aspirin efficacy that could pinpoint individuals who are either sensitive to, or resistant to, the anti–colorectal cancer activity of aspirin (An alternative approach has been to identify genetic variants that may be linked to differential risk reduction associated with aspirin or other nonsteroidal anti-inflammatory drug (NSAID) use (COX-1 and COX-2 enzymes are direct acetylation targets of aspirin, leading to inhibition of downstream synthesis of pro-tumorigenic PGEMoreover, expression of 15-PG dehydrogenase (encoded by Despite the relevance of other genes controlling oxylipin synthesis for the chemopreventative property of aspirin, the relationship between SNP genotypes in a wide range of genes controlling oxylipin synthesis and levels (including The omega-3 PUFA C20:5Several other SNPs that are not directly related to oxylipin metabolism have also been demonstrated to modify colorectal cancer risk reduction associated with aspirin, for example rs6983267 (The seAFOod polyp prevention trial was a 2×2 factorial, randomized, placebo-controlled trial of aspirin 300 mg daily and EPA 2,000 mg free fatty acid equivalents daily, alone or in combination, for 12 months in 707 individuals aged 55–73 years with “high-risk” colorectal polyp findings (≥3 polyps, if one polyp was ≥10 mm; or ≥5 polyps of any size) at screening colonoscopy in the English Bowel Cancer Screening Programme (BCSP; refs. We tested the relationship between SNPs in genes controlling oxylipin synthesis and levels, which are relevant for the putative mechanism(s) of the anticancer activity of aspirin and EPA, as well as SNPs in selected genes already linked to modification of colorectal cancer risk reduction by aspirin, and colorectal polyp outcomes in the seAFOod polyp prevention trial.