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MDPI, Nutrients, 11(13), p. 4164, 2021

DOI: 10.3390/nu13114164



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Salicylic Acid and Risk of Colorectal Cancer: A Two-Sample Mendelian Randomization Study

Journal article published in 2021 by Aayah Nounu, Rebecca C. Richmond, Isobel D. Stewart, Praveen Surendran, Nicholas J. Wareham, Adam Butterworth, Stephanie J. Weinstein ORCID, Demetrius Albanes, John A. Baron, John L. Hopper, Jane C. Figueiredo ORCID, Polly A. Newcomb, Noralane M. Lindor, Graham Casey, Elizabeth A. Platz and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Data provided by SHERPA/RoMEO


Salicylic acid (SA) has observationally been shown to decrease colorectal cancer (CRC) risk. Aspirin (acetylsalicylic acid, that rapidly deacetylates to SA) is an effective primary and secondary chemopreventive agent. Through a Mendelian randomization (MR) approach, we aimed to address whether levels of SA affected CRC risk, stratifying by aspirin use. A two-sample MR analysis was performed using GWAS summary statistics of SA (INTERVAL and EPIC-Norfolk, N = 14,149) and CRC (CCFR, CORECT, GECCO and UK Biobank, 55,168 cases and 65,160 controls). The DACHS study (4410 cases and 3441 controls) was used for replication and stratification of aspirin-use. SNPs proxying SA were selected via three methods: (1) functional SNPs that influence the activity of aspirin-metabolising enzymes; (2) pathway SNPs present in enzymes’ coding regions; and (3) genome-wide significant SNPs. We found no association between functional SNPs and SA levels. The pathway and genome-wide SNPs showed no association between SA and CRC risk (OR: 1.03, 95% CI: 0.84–1.27 and OR: 1.08, 95% CI: 0.86–1.34, respectively). Results remained unchanged upon aspirin use stratification. We found little evidence to suggest that an SD increase in genetically predicted SA protects against CRC risk in the general population and upon stratification by aspirin use.