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GWAS Study

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

Nounu A, Richmond RC, Stewart ID et al.

34836419 PubMed ID
GWAS Study Type
14149 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

NA
Nounu A
RR
Richmond RC
SI
Stewart ID
SP
Surendran P
WN
Wareham NJ
BA
Butterworth A
WS
Weinstein SJ
AD
Albanes D
BJ
Baron JA
HJ
Hopper JL
FJ
Figueiredo JC
NP
Newcomb PA
LN
Lindor NM
CG
Casey G
PE
Platz EA
ML
Marchand LL
UC
Ulrich CM
LC
Li CI
VD
van Dujinhoven FJB
GA
Gsur A
CP
Campbell PT
MV
Moreno V
VP
Vodicka P
VL
Vodickova L
AE
Amitay E
AE
Alwers E
CJ
Chang-Claude J
SL
Sakoda LC
SM
Slattery ML
SR
Schoen RE
GM
Gunter MJ
CS
Castellví-Bel S
KH
Kim HR
KS
Kweon SS
CA
Chan AT
LL
Li L
ZW
Zheng W
BD
Bishop DT
BD
Buchanan DD
GG
Giles GG
GS
Gruber SB
RG
Rennert G
SZ
Stadler ZK
HT
Harrison TA
LY
Lin Y
KT
Keku TO
WM
Woods MO
SC
Schafmayer C
VG
Van Guelpen B
GS
Gallinger S
HH
Hampel H
BS
Berndt SI
PP
Pharoah PDP
LA
Lindblom A
WA
Wolk A
WA
Wu AH
WE
White E
PU
Peters U
DD
Drew DA
SD
Scherer D
BJ
Bermejo JL
BH
Brenner H
HM
Hoffmeister M
WA
Williams AC
RC
Relton CL
Chapter II

Abstract

Summary of the research findings

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.

14,149 individuals

Chapter III

Study Statistics

Key metrics and study information

14149
Total Participants
GWAS
Study Type
No
Replicated
Chapter IV

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