The EPIC-Norfolk Study
Salicylic Acid and Risk of Colorectal Cancer: A Two-Sample Mendelian Randomization Study.
Nutrients 2021 ; 13: .
Nounu A, Richmond RC, Stewart ID, Surendran P, Wareham NJ, Butterworth A, Weinstein SJ, Albanes D, Baron JA, Hopper JL, Figueiredo JC, Newcomb PA, Lindor NM, Casey G, Platz EA, Marchand LL, Ulrich CM, Li CI, van Dujinhoven FJB, Gsur A, Campbell PT, Moreno V, Vodicka P, Vodickova L, Amitay E, Alwers E, Chang-Claude J, Sakoda LC, Slattery ML, Schoen RE, Gunter MJ, Castellví-Bel S, Kim HR, Kweon SS, Chan AT, Li L, Zheng W, Bishop DT, Buchanan DD, Giles GG, Gruber SB, Rennert G, Stadler ZK, Harrison TA, Lin Y, Keku TO, Woods MO, Schafmayer C, Van Guelpen B, Gallinger S, Hampel H, Berndt SI, Pharoah PDP, Lindblom A, Wolk A, Wu AH, White E, Peters U, Drew DA, Scherer D, Bermejo JL, Brenner H, Hoffmeister M, Williams AC, and Relton CL
DOI : 10.3390/nu13114164
PubMed ID : 34836419
PMCID : PMC8620763
URL : https://www.mdpi.com/2072-6643/13/11/4164
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.