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    Nutrients. 2021 Nov 21. pii: nu13114164. doi: 10.3390/nu13114164
    Salicylic Acid and Risk of Colorectal Cancer: A Two-Sample Mendelian Randomization Study.
    Nounu A1,  Richmond RC2,  Stewart ID3,  Surendran P4,  Wareham NJ5,  Butterworth A6,  Weinstein SJ7,  Albanes D8,  Baron JA9,  Hopper JL10,  Figueiredo JC11,  Newcomb PA12,  Lindor NM13,  Casey G14,  Platz EA15,  Marchand LL16,  Ulrich CM17,  Li CI18,  van Dujinhoven FJB19,  Gsur A20,  Campbell PT21,  Moreno V22,  Vodicka P23,  Vodickova L24,  Amitay E25,  Alwers E26,  Chang-Claude J27,  Sakoda LC28,  Slattery ML29,  Schoen RE30,  Gunter MJ31,  Castellví-Bel S32,  Kim HR33,  Kweon SS34,  Chan AT35,  Li L36,  Zheng W37,  Bishop DT38,  Buchanan DD39,  Giles GG40,  Gruber SB41,  Rennert G42,  Stadler ZK43,  Harrison TA44,  Lin Y45,  Keku TO46,  Woods MO47,  Schafmayer C48,  Van Guelpen B49,  Gallinger S50,  Hampel H51,  Berndt SI52,  Pharoah PDP53,  Lindblom A54,  Wolk A55,  Wu AH56,  White E57,  Peters U58,  Drew DA59,  Scherer D60,  Bermejo JL61,  Brenner H62,  Hoffmeister M63,  Williams AC64,  Relton CL65
    Author information
    1Integrative Cancer Epidemiology Programme (ICEP), Medical Research Council (MRC) Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol BS8 2BN, UK.
    2Integrative Cancer Epidemiology Programme (ICEP), Medical Research Council (MRC) Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol BS8 2BN, UK.
    3MRC Epidemiology Unit, School of Clinical Medicine, University of Cambridge, Cambridge CB2 0SL, UK.
    4British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
    5MRC Epidemiology Unit, School of Clinical Medicine, University of Cambridge, Cambridge CB2 0SL, UK.
    6British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
    7Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USA.
    8Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USA.
    9Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, NC 27516, USA.
    10Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC 3053, Australia.
    11Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
    12Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
    13Department of Health Science Research, Mayo Clinic, Scottsdale, AZ 85259, USA.
    14Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA 22908, USA.
    15Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
    16Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
    17Huntsman Cancer Institute, Department of Population Health Sciences, University of Utah, Salt Lake City, UT 84112, USA.
    18Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
    19Division of Human Nutrition and Health, Department of Agrotechnology and Food Sciences, Wageningen University & Research, 6700 HB Wageningen, The Netherlands.
    20Institute of Cancer Research, Department of Medicine I, Medical University Vienna, 1090 Vienna, Austria.
    21Department of Population Science, American Cancer Society, Atlanta, GA 30303, USA.
    22Oncology Data Analytics Program, Catalan Institute of Oncology-IDIBELL, 08908 Barcelona, Spain.
    23Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, 142 20 Prague, Czech Republic.
    24Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, 142 20 Prague, Czech Republic.
    25Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
    26Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
    27Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
    28Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
    29Department of Internal Medicine, University of Utah, Salt Lake City, UT 84112, USA.
    30Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA.
    31Nutrition and Metabolism Section, International Agency for Research on Cancer, World Health Organization, 69372 Lyon, France.
    32Gastroenterology 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.
    33Department of Surgery, Chonnam National University Hwasun Hospital and Medical School, Hwasun 58128, Korea.
    34Department of Preventive Medicine, Chonnam National University Medical School, Gwangju 61186, Korea.
    35Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
    36Department of Family Medicine, University of Virginia, Charlottesville, VA 22903, USA.
    37Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
    38Leeds Institute of Cancer and Pathology, School of Medicine, University of Leeds, Leeds LS2 9JT, UK.
    39Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, VIC 3010, Australia.
    40Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC 3053, Australia.
    41Department of Preventive Medicine & USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
    42Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa 3448516, Israel.
    43Memorial Sloan Kettering Cancer Center, Department of Medicine, New York, NY 10065, USA.
    44Division of Human Nutrition and Health, Department of Agrotechnology and Food Sciences, Wageningen University & Research, 6700 HB Wageningen, The Netherlands.
    45Division of Human Nutrition and Health, Department of Agrotechnology and Food Sciences, Wageningen University & Research, 6700 HB Wageningen, The Netherlands.
    46Center for Gastrointestinal Biology and Disease, School of Medicine, University of North Carolina, Chapel Hill, NC 27599-7555, USA.
    47Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL A1B 3V6, Canada.
    48Department of General Surgery, University Hospital Rostock, 18057 Rostock, Germany.
    49Department of Radiation Sciences, Oncology Unit, Umeå University, 901 87 Umeå, Sweden.
    50Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Faculty of Medicine, University of Toronto, Toronto, ON M5G 1X5, Canada.
    51Division of Human Genetics, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA.
    52Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USA.
    53Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
    54Department of Clinical Genetics, Karolinska University Hospital, 171 64 Solna, Sweden.
    55Institute of Environmental Medicine, Karolinska Institutet, 171 64 Solna, Sweden.
    56Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90032, USA.
    57Division of Human Nutrition and Health, Department of Agrotechnology and Food Sciences, Wageningen University & Research, 6700 HB Wageningen, The Netherlands.
    58Division of Human Nutrition and Health, Department of Agrotechnology and Food Sciences, Wageningen University & Research, 6700 HB Wageningen, The Netherlands.
    59Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
    60Institute of Medical Biometry and Informatics, Medical Faculty, University of Heidelberg, Im Neuenheimer Feld 130.3, 69120 Heidelberg, Germany.
    61Institute of Medical Biometry and Informatics, Medical Faculty, University of Heidelberg, Im Neuenheimer Feld 130.3, 69120 Heidelberg, Germany.
    62Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
    63Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
    64School of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK.
    65Integrative Cancer Epidemiology Programme (ICEP), Medical Research Council (MRC) Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol BS8 2BN, UK.
    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: Mendelian randomization, aspirin, colorectal cancer, salicylic acid

    Publikations ID: 34836419
    Quelle: öffnen
     
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