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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2021-11-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/13/11/4164 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T05:11:23Z |
| format | Article |
| id | doaj.art-e30a5ff9584c4ac6a79691fbd1a22a9a |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-10T05:11:23Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-e30a5ff9584c4ac6a79691fbd1a22a9a2023-11-23T00:51:38ZengMDPI AGNutrients2072-66432021-11-011311416410.3390/nu13114164Salicylic Acid and Risk of Colorectal Cancer: A Two-Sample Mendelian Randomization StudyAayah Nounu0Rebecca C. Richmond1Isobel D. Stewart2Praveen Surendran3Nicholas J. Wareham4Adam Butterworth5Stephanie J. Weinstein6Demetrius Albanes7John A. Baron8John L. Hopper9Jane C. Figueiredo10Polly A. Newcomb11Noralane M. Lindor12Graham Casey13Elizabeth A. Platz14Loïc Le Marchand15Cornelia M. Ulrich16Christopher I. Li17Fränzel J. B. van Dujinhoven18Andrea Gsur19Peter T. Campbell20Víctor Moreno21Pavel Vodicka22Ludmila Vodickova23Efrat Amitay24Elizabeth Alwers25Jenny Chang-Claude26Lori C. Sakoda27Martha L. Slattery28Robert E. Schoen29Marc J. Gunter30Sergi Castellví-Bel31Hyeong-Rok Kim32Sun-Seog Kweon33Andrew T. Chan34Li Li35Wei Zheng36D. Timothy Bishop37Daniel D. Buchanan38Graham G. Giles39Stephen B. Gruber40Gad Rennert41Zsofia K. Stadler42Tabitha A. Harrison43Yi Lin44Temitope O. Keku45Michael O. Woods46Clemens Schafmayer47Bethany Van Guelpen48Steven Gallinger49Heather Hampel50Sonja I. Berndt51Paul D. P. Pharoah52Annika Lindblom53Alicja Wolk54Anna H. Wu55Emily White56Ulrike Peters57David A. Drew58Dominique Scherer59Justo Lorenzo Bermejo60Hermann Brenner61Michael Hoffmeister62Ann C. Williams63Caroline L. Relton64Integrative Cancer Epidemiology Programme (ICEP), Medical Research Council (MRC) Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol BS8 2BN, UKIntegrative Cancer Epidemiology Programme (ICEP), Medical Research Council (MRC) Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol BS8 2BN, UKMRC Epidemiology Unit, School of Clinical Medicine, University of Cambridge, Cambridge CB2 0SL, UKBritish Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UKMRC Epidemiology Unit, School of Clinical Medicine, University of Cambridge, Cambridge CB2 0SL, UKBritish Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UKDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USADivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USADepartment of Medicine, School of Medicine, University of North Carolina, Chapel Hill, NC 27516, USACentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC 3053, AustraliaDepartment of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USAPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USADepartment of Health Science Research, Mayo Clinic, Scottsdale, AZ 85259, USACenter for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA 22908, USADepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USACancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USAHuntsman Cancer Institute, Department of Population Health Sciences, University of Utah, Salt Lake City, UT 84112, USAPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USADivision of Human Nutrition and Health, Department of Agrotechnology and Food Sciences, Wageningen University & Research, 6700 HB Wageningen, The NetherlandsInstitute of Cancer Research, Department of Medicine I, Medical University Vienna, 1090 Vienna, AustriaDepartment of Population Science, American Cancer Society, Atlanta, GA 30303, USAOncology Data Analytics Program, Catalan Institute of Oncology-IDIBELL, 08908 Barcelona, SpainDepartment of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, 142 20 Prague, Czech RepublicDepartment of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, 142 20 Prague, Czech RepublicDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, GermanyDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, GermanyDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, GermanyPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USADepartment of Internal Medicine, University of Utah, Salt Lake City, UT 84112, USADepartment of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USANutrition and Metabolism Section, International Agency for Research on Cancer, World Health Organization, 69372 Lyon, FranceGastroenterology Department, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, 08036 Barcelona, SpainDepartment of Surgery, Chonnam National University Hwasun Hospital and Medical School, Hwasun 58128, KoreaDepartment of Preventive Medicine, Chonnam National University Medical School, Gwangju 61186, KoreaDivision of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USADepartment of Family Medicine, University of Virginia, Charlottesville, VA 22903, USADivision of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USALeeds Institute of Cancer and Pathology, School of Medicine, University of Leeds, Leeds LS2 9JT, UKColorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, VIC 3010, AustraliaCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC 3053, AustraliaDepartment of Preventive Medicine & USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USADepartment of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa 3448516, IsraelMemorial Sloan Kettering Cancer Center, Department of Medicine, New York, NY 10065, USADivision of Human Nutrition and Health, Department of Agrotechnology and Food Sciences, Wageningen University & Research, 6700 HB Wageningen, The NetherlandsDivision of Human Nutrition and Health, Department of Agrotechnology and Food Sciences, Wageningen University & Research, 6700 HB Wageningen, The NetherlandsCenter for Gastrointestinal Biology and Disease, School of Medicine, University of North Carolina, Chapel Hill, NC 27599-7555, USADiscipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL A1B 3V6, CanadaDepartment of General Surgery, University Hospital Rostock, 18057 Rostock, GermanyDepartment of Radiation Sciences, Oncology Unit, Umeå University, 901 87 Umeå, SwedenLunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Faculty of Medicine, University of Toronto, Toronto, ON M5G 1X5, CanadaDivision of Human Genetics, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USADivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USADepartment of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UKDepartment of Clinical Genetics, Karolinska University Hospital, 171 64 Solna, SwedenInstitute of Environmental Medicine, Karolinska Institutet, 171 64 Solna, SwedenDepartment of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90032, USADivision of Human Nutrition and Health, Department of Agrotechnology and Food Sciences, Wageningen University & Research, 6700 HB Wageningen, The NetherlandsDivision of Human Nutrition and Health, Department of Agrotechnology and Food Sciences, Wageningen University & Research, 6700 HB Wageningen, The NetherlandsChanning Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USAInstitute of Medical Biometry and Informatics, Medical Faculty, University of Heidelberg, Im Neuenheimer Feld 130.3, 69120 Heidelberg, GermanyInstitute of Medical Biometry and Informatics, Medical Faculty, University of Heidelberg, Im Neuenheimer Feld 130.3, 69120 Heidelberg, GermanyDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, GermanyDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, GermanySchool of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UKIntegrative Cancer Epidemiology Programme (ICEP), Medical Research Council (MRC) Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol BS8 2BN, UKSalicylic 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.https://www.mdpi.com/2072-6643/13/11/4164salicylic acidaspirincolorectal cancerMendelian randomization |
| spellingShingle | 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 Nutrients salicylic acid aspirin colorectal cancer Mendelian randomization |
| title | 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_short | 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 |
| topic | salicylic acid aspirin colorectal cancer Mendelian randomization |
| url | https://www.mdpi.com/2072-6643/13/11/4164 |
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