Journal article
Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent: a Mendelian randomization study
The American journal of clinical nutrition, Vol.113(6), pp.1490-1502
06/01/2021
DOI: 10.1093/ajcn/nqab003
PMCID: PMC8168352
PMID: 33740060
Abstract
The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited.
To complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR).
Two-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions.
Nominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer [ORs per SD (ORSD): 1.08; 95% CI: 1.00, 1.17; P value = 0.05] and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12; 95% CI: 1.03, 1.21; P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98; 95% CI: 0.96, 1.00; P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of β-carotene, calcium, copper, folate, magnesium, phosphorus, and vitamin B-6 were not associated with disease risk.
These results suggest possible causal associations of circulating iron and vitamin B-12 (positively) and selenium (inversely) with risk of colon cancer.
Details
- Title: Subtitle
- Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent: a Mendelian randomization study
- Creators
- Konstantinos K Tsilidis - Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United KingdomLinda Snetselaar - Department of Epidemiology, University of Iowa College of Public Health, Iowa City, IA, USANikos Papadimitriou - Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, FranceNiki Dimou - Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, FranceDipender Gill - Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United KingdomSarah J Lewis - Medical Research Council Integrative Epidemiology Unit, Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United KingdomRichard M Martin - University Hospitals Bristol National Health Service Foundation Trust National Institute for Health Research Bristol Biomedical Research Centre, University of Bristol, Bristol, United KingdomNeil Murphy - Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, FranceGeorgios Markozannes - Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, GreeceAmanda J Cross - Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United KingdomKimberley Burrows - Medical Research Council Integrative Epidemiology Unit, Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United KingdomDavid S Lopez - Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, Galveston, TX, USATimothy J Key - Nuffield Department of Population Health, University of Oxford, Oxford, United KingdomRuth C Travis - Nuffield Department of Population Health, University of Oxford, Oxford, United KingdomAurora Perez-Cornago - Nuffield Department of Population Health, University of Oxford, Oxford, United KingdomDavid J Hunter - Nuffield Department of Population Health, University of Oxford, Oxford, United KingdomFränzel J B van Duijnhoven - Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, NetherlandsDemetrius Albanes - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USAVolker Arndt - Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, GermanySonja I Berndt - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USAStéphane Bézieau - Medical Genetics Service, University Hospital Center (CHU) Nantes, Nantes, FranceD Timothy Bishop - , Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, United KingdomJuergen Boehm - Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USAHermann Brenner - German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, GermanyAndrea Burnett-Hartman - Institute for Health Research, Kaiser Permanente Colorado, Denver, CO, USAPeter T Campbell - Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA, USAGraham Casey - Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USASergi Castellví-Bel - Gastroenterology Department, Hospital Clinic, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Biomedical Research Network Center for Liver and Digestive Diseases (CIBEREHD), University of Barcelona, Barcelona, SpainAndrew T Chan - Department of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Harvard University, Boston, MA, USAJenny Chang-Claude - University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg, Hamburg, GermanyAlbert de la Chapelle - Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USAJane C Figueiredo - Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USASteven J Gallinger - Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, CanadaGraham G Giles - Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, AustraliaPhyllis J Goodman - SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USAAndrea Gsur - Institute of Cancer Research, Department of Medicine I, Medical University Vienna, Vienna, AustriaJochen Hampe - Department of Medicine I, University Hospital Dresden, Dresden University of Technology (TU Dresden), Dresden, GermanyHeather Hampel - Division of Human Genetics, Department of Internal Medicine, The Ohio State University, Columbus, OH, USAMichael Hoffmeister - Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, GermanyMark A Jenkins - Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, AustraliaTemitope O Keku - Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USASun-Seog Kweon - Jeonnam Regional Cancer Center, Chonnam National University Hwasun Hospital, Hwasun, Republic of KoreaSusanna C Larsson - Institute of Environmental Medicine, Karolinska Institute, Stockholm, SwedenLoic Le Marchand - University of Hawaii Cancer Center, Honolulu, HI, USAChristopher I Li - Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USALi Li - Department of Family Medicine, University of Virginia, Charlottesville, VA, USAAnnika Lindblom - Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, SwedenVicente Martín - Biomedicine Institute (IBIOMED), University of León, León, SpainRoger L Milne - Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, AustraliaVictor Moreno - ONCOBEL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, SpainHongmei Nan - IU Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN, USARami Nassir - Department of Pathology, School of Medicine, Umm Al-Qura'a University, Mecca, Saudi ArabiaPolly A Newcomb - School of Public Health, University of Washington, Seattle, WA, USAKenneth Offit - Department of Medicine, Weill Cornell Medical College, New York, NY, USAPaul D P Pharoah - Department of Public Health and Primary Care, University of Cambridge, Cambridge, United KingdomElizabeth A Platz - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USAJohn D Potter - Centre for Public Health Research, Massey University, Wellington, New ZealandLihong Qi - Department of Public Health Sciences, School of Medicine, University of California Davis, Davis, CA, USAGad Rennert - Clalit National Cancer Control Center, Haifa, IsraelLori C Sakoda - Division of Research, Kaiser Permanente Northern California, Oakland, CA, USAClemens Schafmayer - Department of General Surgery, University Hospital Rostock, Rostock, GermanyMartha L Slattery - Department of Internal Medicine, University of Utah, Salt Lake City, UT, USAJeanette Schenk - SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USAStephen N Thibodeau - Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USACornelia M Ulrich - Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USABethany Van Guelpen - Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, SwedenSophia Harlid - Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, SwedenKala Visvanathan - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USALudmila Vodickova - Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech RepublicHansong Wang - University of Hawaii Cancer Center, Honolulu, HI, USAEmily White - Department of Epidemiology, University of Washington, Seattle, WA, USAAlicja Wolk - Institute of Environmental Medicine, Karolinska Institute, Stockholm, SwedenMichael O Woods - Discipline of Genetics, Memorial University of Newfoundland, St. John's, Newfoundland, CanadaAnna H Wu - Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USAWei Zheng - Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN, USABas Bueno-de-Mesquita - Formerly, Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, NetherlandsMarie-Christine Boutron-Ruault - Centre for Research in Epidemiology and Population Health (CESP), Gustave Roussy, Villejuif, FranceDavid J Hughes - Cancer Biology and Therapeutics Group, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, IrelandPaula Jakszyn - Blanquerna Faculty of Health Sciences, Ramon Llull University, Barcelona, SpainDomenico Palli - Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network-ISPRO, Florence, ItalyTilman Kühn - Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, GermanyElio Riboli - Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United KingdomEdward L Giovannucci - Department of Nutrition, Harvard TH Chan School of Public Health, Harvard University, Boston, MA, USABarbara L Banbury - Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USAStephen B Gruber - USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USAUlrike Peters - Department of Epidemiology, University of Washington, Seattle, WA, USAMarc J Gunter - Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, FranceGenetics and Epidemiology of Colorectal Cancer Consortium (GECCO)Colorectal Cancer Transdisciplinary Study (CORECT)Colon Cancer Family Registry (CCFR)
- Resource Type
- Journal article
- Publication Details
- The American journal of clinical nutrition, Vol.113(6), pp.1490-1502
- DOI
- 10.1093/ajcn/nqab003
- PMID
- 33740060
- PMCID
- PMC8168352
- ISSN
- 0002-9165
- eISSN
- 1938-3207
- Grant note
- MC_UU_12013/2 / Medical Research Council U01 CA206110 / NCI NIH HHS C18281/A19169 / Cancer Research UK MC_UU_12013/3 / Medical Research Council MC_UU_12013/1 / Medical Research Council P30 CA016086 / NCI NIH HHS P30 CA015083 / NCI NIH HHS U01 CA167551 / NCI NIH HHS
- Language
- English
- Date published
- 06/01/2021
- Academic Unit
- Epidemiology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984215142402771
Metrics
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