Nutrients (Nov 2021)
Salicylic Acid and Risk of Colorectal Cancer: A Two-Sample Mendelian Randomization Study
- 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
Affiliations
- Aayah Nounu
- Integrative Cancer Epidemiology Programme (ICEP), Medical Research Council (MRC) Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol BS8 2BN, UK
- Rebecca C. Richmond
- Integrative Cancer Epidemiology Programme (ICEP), Medical Research Council (MRC) Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol BS8 2BN, UK
- Isobel D. Stewart
- MRC Epidemiology Unit, School of Clinical Medicine, University of Cambridge, Cambridge CB2 0SL, UK
- Praveen Surendran
- British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK
- Nicholas J. Wareham
- MRC Epidemiology Unit, School of Clinical Medicine, University of Cambridge, Cambridge CB2 0SL, UK
- Adam Butterworth
- British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK
- Stephanie J. Weinstein
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USA
- Demetrius Albanes
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USA
- John A. Baron
- Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, NC 27516, USA
- John L. Hopper
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC 3053, Australia
- Jane C. Figueiredo
- Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- Polly A. Newcomb
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA
- Noralane M. Lindor
- Department of Health Science Research, Mayo Clinic, Scottsdale, AZ 85259, USA
- Graham Casey
- Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA 22908, USA
- Elizabeth A. Platz
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
- Loïc Le Marchand
- Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA
- Cornelia M. Ulrich
- Huntsman Cancer Institute, Department of Population Health Sciences, University of Utah, Salt Lake City, UT 84112, USA
- Christopher I. Li
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA
- Fränzel J. B. van Dujinhoven
- Division of Human Nutrition and Health, Department of Agrotechnology and Food Sciences, Wageningen University & Research, 6700 HB Wageningen, The Netherlands
- Andrea Gsur
- Institute of Cancer Research, Department of Medicine I, Medical University Vienna, 1090 Vienna, Austria
- Peter T. Campbell
- Department of Population Science, American Cancer Society, Atlanta, GA 30303, USA
- Víctor Moreno
- Oncology Data Analytics Program, Catalan Institute of Oncology-IDIBELL, 08908 Barcelona, Spain
- Pavel Vodicka
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, 142 20 Prague, Czech Republic
- Ludmila Vodickova
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, 142 20 Prague, Czech Republic
- Efrat Amitay
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- Elizabeth Alwers
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- Jenny Chang-Claude
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- Lori C. Sakoda
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA
- Martha L. Slattery
- Department of Internal Medicine, University of Utah, Salt Lake City, UT 84112, USA
- Robert E. Schoen
- Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA
- Marc J. Gunter
- Nutrition and Metabolism Section, International Agency for Research on Cancer, World Health Organization, 69372 Lyon, France
- Sergi Castellví-Bel
- Gastroenterology 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, Spain
- Hyeong-Rok Kim
- Department of Surgery, Chonnam National University Hwasun Hospital and Medical School, Hwasun 58128, Korea
- Sun-Seog Kweon
- Department of Preventive Medicine, Chonnam National University Medical School, Gwangju 61186, Korea
- Andrew T. Chan
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
- Li Li
- Department of Family Medicine, University of Virginia, Charlottesville, VA 22903, USA
- Wei Zheng
- Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
- D. Timothy Bishop
- Leeds Institute of Cancer and Pathology, School of Medicine, University of Leeds, Leeds LS2 9JT, UK
- Daniel D. Buchanan
- Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, VIC 3010, Australia
- Graham G. Giles
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC 3053, Australia
- Stephen B. Gruber
- Department of Preventive Medicine & USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
- Gad Rennert
- Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa 3448516, Israel
- Zsofia K. Stadler
- Memorial Sloan Kettering Cancer Center, Department of Medicine, New York, NY 10065, USA
- Tabitha A. Harrison
- Division of Human Nutrition and Health, Department of Agrotechnology and Food Sciences, Wageningen University & Research, 6700 HB Wageningen, The Netherlands
- Yi Lin
- Division of Human Nutrition and Health, Department of Agrotechnology and Food Sciences, Wageningen University & Research, 6700 HB Wageningen, The Netherlands
- Temitope O. Keku
- Center for Gastrointestinal Biology and Disease, School of Medicine, University of North Carolina, Chapel Hill, NC 27599-7555, USA
- Michael O. Woods
- Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL A1B 3V6, Canada
- Clemens Schafmayer
- Department of General Surgery, University Hospital Rostock, 18057 Rostock, Germany
- Bethany Van Guelpen
- Department of Radiation Sciences, Oncology Unit, Umeå University, 901 87 Umeå, Sweden
- Steven Gallinger
- Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Faculty of Medicine, University of Toronto, Toronto, ON M5G 1X5, Canada
- Heather Hampel
- Division of Human Genetics, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA
- Sonja I. Berndt
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USA
- Paul D. P. Pharoah
- Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK
- Annika Lindblom
- Department of Clinical Genetics, Karolinska University Hospital, 171 64 Solna, Sweden
- Alicja Wolk
- Institute of Environmental Medicine, Karolinska Institutet, 171 64 Solna, Sweden
- Anna H. Wu
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90032, USA
- Emily White
- Division of Human Nutrition and Health, Department of Agrotechnology and Food Sciences, Wageningen University & Research, 6700 HB Wageningen, The Netherlands
- Ulrike Peters
- Division of Human Nutrition and Health, Department of Agrotechnology and Food Sciences, Wageningen University & Research, 6700 HB Wageningen, The Netherlands
- David A. Drew
- Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
- Dominique Scherer
- Institute of Medical Biometry and Informatics, Medical Faculty, University of Heidelberg, Im Neuenheimer Feld 130.3, 69120 Heidelberg, Germany
- Justo Lorenzo Bermejo
- Institute of Medical Biometry and Informatics, Medical Faculty, University of Heidelberg, Im Neuenheimer Feld 130.3, 69120 Heidelberg, Germany
- Hermann Brenner
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- Michael Hoffmeister
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- Ann C. Williams
- School of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK
- Caroline L. Relton
- Integrative Cancer Epidemiology Programme (ICEP), Medical Research Council (MRC) Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol BS8 2BN, UK
- DOI
- https://doi.org/10.3390/nu13114164
- Journal volume & issue
-
Vol. 13,
no. 11
p. 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.
Keywords
