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AFPPS, Aspirin/Folate Polyp Prevention Study; CI, confidence interval; CRC, colorectal cancer; GWAS, genome-wide association study; HPGD, 15-hydroxyprostaglandin dehydrogenase; HR, hazard ratio; IHC, immunohistochemistry; MIC1, macrophage inhibitory cytokine 1; mt, mutant; NSAID, non-steroidal anti-inflammatory drug; PGE-M, major metabolite of prostaglandin E2; PIK3CA, PI3K catalytic subunit-α; PTGS2, prostaglandin-endoperoxide synthase 2; RCT, randomized clinical trial; RR, relative risk; SNP, single nucleotide polymorphism; sTNFR2, soluble tumour necrosis factor receptor 2; wt, wild-type. *All estimates are based on multivariable adjusted models. ‡Ten cohorts: CCFR, Colon Cancer Family Registry; DACHS, Darmkrebs: Chancen der Verhütung durch Screening Study; DALS, Diet, Activity and Lifestyle Study; HPFS, Health Professionals Follow-up Study; NHS, Nurses' Health Study; OFCCR, Ontario Familial Colorectal Cancer Registry; PMH-CCFR, Postmenopausal Hormone Study–CCFR; PLCO, Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial; VITAL, Vitamins and Lifestyle; WHI, Women's Health Initiative. §Case-only interaction analysis; ||RR represents 81 mg aspirin versus placebo. No significant effect was measured for 325 mg aspirin.