Salicylic Acid and Risk of Colorectal Cancer: A Two-Sample Mendelian Randomization Study.
Authors
Nounu, Aayah
Richmond, Rebecca C
Stewart, Isobel
Surendran, Praveen
Albanes, Demetrius
Baron, John A
Hopper, John L
Newcomb, Polly A
Lindor, Noralane M
Casey, Graham
Platz, Elizabeth A
Li, Christopher I
van Dujinhoven, Fränzel JB
Campbell, Peter T
Vodicka, Pavel
Vodickova, Ludmila
Amitay, Efrat
Alwers, Elizabeth
Chang-Claude, Jenny
Slattery, Martha L
Schoen, Robert E
Gunter, Marc J
Kim, Hyeong-Rok
Kweon, Sun-Seog
Chan, Andrew T
Li, Li
Zheng, Wei
Bishop, D Timothy
Giles, Graham G
Gruber, Stephen B
Rennert, Gad
Stadler, Zsofia K
Harrison, Tabitha A
Lin, Yi
Keku, Temitope O
Woods, Michael O
Schafmayer, Clemens
Van Guelpen, Bethany
Gallinger, Steven
Hampel, Heather
Berndt, Sonja I
Lindblom, Annika
Wolk, Alicja
Wu, Anna H
White, Emily
Peters, Ulrike
Drew, David A
Scherer, Dominique
Brenner, Hermann
Williams, Ann C
Relton, Caroline L
Publication Date
2021-11-21Journal Title
Nutrients
ISSN
2072-6643
Publisher
MDPI AG
Volume
13
Issue
11
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Nounu, A., Richmond, R. C., Stewart, I., Surendran, P., Wareham, N., Butterworth, A., Weinstein, S. J., et al. (2021). Salicylic Acid and Risk of Colorectal Cancer: A Two-Sample Mendelian Randomization Study.. Nutrients, 13 (11) https://doi.org/10.3390/nu13114164
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.
Keywords
salicylic acid, aspirin, colorectal cancer, Mendelian randomization
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)
Identifiers
External DOI: https://doi.org/10.3390/nu13114164
This record's URL: https://www.repository.cam.ac.uk/handle/1810/330937
Rights
Licence:
https://creativecommons.org/licenses/by/4.0/
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