Salicylic Acid and Risk of Colorectal Cancer: A Two-Sample Mendelian Randomization Study
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 level...
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2021
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oai:doaj.org-article:e30a5ff9584c4ac6a79691fbd1a22a9a2021-11-25T18:37:15ZSalicylic Acid and Risk of Colorectal Cancer: A Two-Sample Mendelian Randomization Study10.3390/nu131141642072-6643https://doaj.org/article/e30a5ff9584c4ac6a79691fbd1a22a9a2021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6643/13/11/4164https://doaj.org/toc/2072-6643Salicylic 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.Aayah NounuRebecca C. RichmondIsobel D. StewartPraveen SurendranNicholas J. WarehamAdam ButterworthStephanie J. WeinsteinDemetrius AlbanesJohn A. BaronJohn L. HopperJane C. FigueiredoPolly A. NewcombNoralane M. LindorGraham CaseyElizabeth A. PlatzLoïc Le MarchandCornelia M. UlrichChristopher I. LiFränzel J. B. van DujinhovenAndrea GsurPeter T. CampbellVíctor MorenoPavel VodickaLudmila VodickovaEfrat AmitayElizabeth AlwersJenny Chang-ClaudeLori C. SakodaMartha L. SlatteryRobert E. SchoenMarc J. GunterSergi Castellví-BelHyeong-Rok KimSun-Seog KweonAndrew T. ChanLi LiWei ZhengD. Timothy BishopDaniel D. BuchananGraham G. GilesStephen B. GruberGad RennertZsofia K. StadlerTabitha A. HarrisonYi LinTemitope O. KekuMichael O. WoodsClemens SchafmayerBethany Van GuelpenSteven GallingerHeather HampelSonja I. BerndtPaul D. P. PharoahAnnika LindblomAlicja WolkAnna H. WuEmily WhiteUlrike PetersDavid A. DrewDominique SchererJusto Lorenzo BermejoHermann BrennerMichael HoffmeisterAnn C. WilliamsCaroline L. ReltonMDPI AGarticlesalicylic acidaspirincolorectal cancerMendelian randomizationNutrition. Foods and food supplyTX341-641ENNutrients, Vol 13, Iss 4164, p 4164 (2021) |
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salicylic acid aspirin colorectal cancer Mendelian randomization Nutrition. Foods and food supply TX341-641 |
| spellingShingle |
salicylic acid aspirin colorectal cancer Mendelian randomization Nutrition. Foods and food supply TX341-641 Aayah Nounu Rebecca C. Richmond Isobel D. Stewart Praveen Surendran Nicholas J. Wareham Adam Butterworth Stephanie J. Weinstein Demetrius Albanes John A. Baron John L. Hopper Jane C. Figueiredo Polly A. Newcomb Noralane M. Lindor Graham Casey Elizabeth A. Platz Loïc Le Marchand Cornelia M. Ulrich Christopher I. Li Fränzel J. B. van Dujinhoven Andrea Gsur Peter T. Campbell Víctor Moreno Pavel Vodicka Ludmila Vodickova Efrat Amitay Elizabeth Alwers Jenny Chang-Claude Lori C. Sakoda Martha L. Slattery Robert E. Schoen Marc J. Gunter Sergi Castellví-Bel Hyeong-Rok Kim Sun-Seog Kweon Andrew T. Chan Li Li Wei Zheng D. Timothy Bishop Daniel D. Buchanan Graham G. Giles Stephen B. Gruber Gad Rennert Zsofia K. Stadler Tabitha A. Harrison Yi Lin Temitope O. Keku Michael O. Woods Clemens Schafmayer Bethany Van Guelpen Steven Gallinger Heather Hampel Sonja I. Berndt Paul D. P. Pharoah Annika Lindblom Alicja Wolk Anna H. Wu Emily White Ulrike Peters David A. Drew Dominique Scherer Justo Lorenzo Bermejo Hermann Brenner Michael Hoffmeister Ann C. Williams Caroline L. Relton Salicylic Acid and Risk of Colorectal Cancer: A Two-Sample Mendelian Randomization Study |
| description |
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. |
| format |
article |
| author |
Aayah Nounu Rebecca C. Richmond Isobel D. Stewart Praveen Surendran Nicholas J. Wareham Adam Butterworth Stephanie J. Weinstein Demetrius Albanes John A. Baron John L. Hopper Jane C. Figueiredo Polly A. Newcomb Noralane M. Lindor Graham Casey Elizabeth A. Platz Loïc Le Marchand Cornelia M. Ulrich Christopher I. Li Fränzel J. B. van Dujinhoven Andrea Gsur Peter T. Campbell Víctor Moreno Pavel Vodicka Ludmila Vodickova Efrat Amitay Elizabeth Alwers Jenny Chang-Claude Lori C. Sakoda Martha L. Slattery Robert E. Schoen Marc J. Gunter Sergi Castellví-Bel Hyeong-Rok Kim Sun-Seog Kweon Andrew T. Chan Li Li Wei Zheng D. Timothy Bishop Daniel D. Buchanan Graham G. Giles Stephen B. Gruber Gad Rennert Zsofia K. Stadler Tabitha A. Harrison Yi Lin Temitope O. Keku Michael O. Woods Clemens Schafmayer Bethany Van Guelpen Steven Gallinger Heather Hampel Sonja I. Berndt Paul D. P. Pharoah Annika Lindblom Alicja Wolk Anna H. Wu Emily White Ulrike Peters David A. Drew Dominique Scherer Justo Lorenzo Bermejo Hermann Brenner Michael Hoffmeister Ann C. Williams Caroline L. Relton |
| author_facet |
Aayah Nounu Rebecca C. Richmond Isobel D. Stewart Praveen Surendran Nicholas J. Wareham Adam Butterworth Stephanie J. Weinstein Demetrius Albanes John A. Baron John L. Hopper Jane C. Figueiredo Polly A. Newcomb Noralane M. Lindor Graham Casey Elizabeth A. Platz Loïc Le Marchand Cornelia M. Ulrich Christopher I. Li Fränzel J. B. van Dujinhoven Andrea Gsur Peter T. Campbell Víctor Moreno Pavel Vodicka Ludmila Vodickova Efrat Amitay Elizabeth Alwers Jenny Chang-Claude Lori C. Sakoda Martha L. Slattery Robert E. Schoen Marc J. Gunter Sergi Castellví-Bel Hyeong-Rok Kim Sun-Seog Kweon Andrew T. Chan Li Li Wei Zheng D. Timothy Bishop Daniel D. Buchanan Graham G. Giles Stephen B. Gruber Gad Rennert Zsofia K. Stadler Tabitha A. Harrison Yi Lin Temitope O. Keku Michael O. Woods Clemens Schafmayer Bethany Van Guelpen Steven Gallinger Heather Hampel Sonja I. Berndt Paul D. P. Pharoah Annika Lindblom Alicja Wolk Anna H. Wu Emily White Ulrike Peters David A. Drew Dominique Scherer Justo Lorenzo Bermejo Hermann Brenner Michael Hoffmeister Ann C. Williams Caroline L. Relton |
| author_sort |
Aayah Nounu |
| title |
Salicylic Acid and Risk of Colorectal Cancer: A Two-Sample Mendelian Randomization Study |
| title_short |
Salicylic Acid and Risk of Colorectal Cancer: A Two-Sample Mendelian Randomization Study |
| title_full |
Salicylic Acid and Risk of Colorectal Cancer: A Two-Sample Mendelian Randomization Study |
| title_fullStr |
Salicylic Acid and Risk of Colorectal Cancer: A Two-Sample Mendelian Randomization Study |
| title_full_unstemmed |
Salicylic Acid and Risk of Colorectal Cancer: A Two-Sample Mendelian Randomization Study |
| title_sort |
salicylic acid and risk of colorectal cancer: a two-sample mendelian randomization study |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/e30a5ff9584c4ac6a79691fbd1a22a9a |
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