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

Published version
Peer-reviewed

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Authors

Nounu, Aayah 
Richmond, Rebecca C 
Stewart, Isobel D 
Surendran, Praveen 
Wareham, Nicholas J 

Abstract

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.

Description

Keywords

Mendelian randomization, aspirin, colorectal cancer, salicylic acid, Aspirin, Case-Control Studies, Colorectal Neoplasms, Diet, Female, Genome-Wide Association Study, Genotyping Techniques, Humans, Male, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, Risk Factors, Salicylic Acid

Journal Title

Nutrients

Conference Name

Journal ISSN

2072-6643
2072-6643

Volume Title

13

Publisher

MDPI AG
Sponsorship
Medical Research Council (MC_UU_12015/1)
MRC (MC_UU_00006/1)
Medical Research Council (MR/N003284/1)
British Heart Foundation (None)
British Heart Foundation (CH/12/2/29428)
British Heart Foundation (RG/18/13/33946)
Medical Research Council (MR/S003746/1)
Medical Research Council (G1000143)
Medical Research Council (G0401527)
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