NSAID use effect on colorectal cancer risk influenced by genetics

1. This study found that the regular use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), or both was associated with a decreased risk of colorectal cancer.

2. Two single nucleotide polymorphisms (SNPs) were highly correlated with the association between NSAIDs and colon cancer risk.

Evidence Rating Level: 3 (Average)

Study Rundown: Genetic sequencing is being utilized to help predict a patient’s response to drug therapy. While the association between NSAIDs and decreased risk of colorectal cancer has been previously demonstrated, prior genetic studies have attempted to identify underlying genetic markers by assessing individual genes. This study used a broader approach by utilizing genome wide analysis to identify genetic markers that correlate with the effect NSAID use has on colon cancer risk.

This study found that the SNP rs2965667-TT, found in 96% of the population, had the strongest correlation with NSAIDs and colorectal cancer risk. The SNP rs10505806 demonstrated a more limited interaction. A higher risk was observed among the small proportion of the population with rs2965667 TA or AA genotypes and the small proportion with rs10505806 AT or TT genotypes. Major strengths of this study include the large sample size and its use of genome-wide analysis, as opposed to selecting for certain candidate genes to study.

Click to read the study, published today in JAMA

Click to read the accompanying editorial in JAMA

Relevant Reading: Characterization of gene–environment interactions for colorectal cancer susceptibility loci

In-Depth [case-control study]: This study evaluated 8634 colorectal cancer cases and 8553 controls of European descent. Regular use of aspirin and NSAIDs was associated with a lower risk of colorectal cancer compared with nonregular use (prevalence 28% vs. 38%; OR 0.69; 95%CI 0.64-0.74; p = 6.2×10⁻²⁸). SNP rs2965667, at chromosome 12p12.3, showed a genome-wide significant interaction with regular use of aspirin, NSAIDs, or both (p = 4.6×10⁻⁹ for interaction). SNP rs10505806 showed a more limited interaction (p = 5.5×10⁻⁸ for interaction). Compared with nonregular use, regular use of aspirin, NSAIDs, or both was significantly associated with lower risk of colorectal cancer among individuals with rs2965667-TT genotype (prevalence 28% vs. 38%; OR 0.66; 95%CI 0.61-0.70; p = 7.7×10⁻³³). A higher risk was seen among the 4% (n = 722) of the population with the TA or AA genotypes (prevalence 35% vs 29%; OR 1.89; 95%CI 1.27-2.81; p = 0.002)

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