Association of aspirin and NSAID use with risk of colorectal cancer according to genetic variants.

摘要: Importance Use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with lower risk colorectal cancer. Objective To identify common genetic markers that may confer differential benefit from or NSAID chemoprevention, we tested gene × environment interactions between regular use and/or NSAIDs single-nucleotide polymorphisms (SNPs) in relation to Design, Setting, Participants Case-control study using data 5 case-control cohort studies initiated 1976 2003 across the United States, Canada, Australia, Germany including cancer cases (n=8634) matched controls (n=8553) ascertained 2011. were all European descent. Exposures Genome-wide SNP information on factors. Main Outcomes Measures Colorectal Results Regular was (prevalence, 28% vs 38%; odds ratio [OR], 0.69 [95% CI, 0.64-0.74]; P  = 6.2 × 10 −28 ) compared nonregular use. In conventional logistic regression analysis, rs2965667 at chromosome 12p12.3 near MGST1 gene showed a genome-wide significant interaction (  = 4.6 × 10 −9 for interaction). Aspirin among individuals rs2965667-TT genotype OR, 0.66 0.61-0.70];  = 7.7 × 10 −33 but higher those rare (4%) TA AA genotypes 35% 29%; 1.89 1.27-2.81];  = .002). case-only rs16973225 15q25.2 IL16  = 8.2 × 10 rs16973225-AA 0.62-0.71];  = 1.9 × 10 −30 not less (9%) AC CC 36% 39%; 0.97 0.78-1.20];  = .76). Conclusions Relevance this investigation interactions, cancer, association differed according variation 2 SNPs chromosomes 12 15. Validation these findings additional populations facilitate targeted prevention strategies.