Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent: a Mendelian randomization study

Konstantinos K Tsilidis; Nikos Papadimitriou; Niki Dimou; Dipender Gill; Sarah J Lewis; Richard M Martin; Neil Murphy; Georgios Markozannes; Verena Zuber; Amanda J Cross; Kimberley Burrows; David S Lopez; Timothy J Key; Ruth C Travis; Aurora Perez-Cornago; David J Hunter; Fränzel JB van Duijnhoven; Demetrius Albanes; Volker Arndt; Sonja I Berndt; Stéphane Bézieau; D Timothy Bishop; Juergen Boehm; Hermann Brenner; Andrea Burnett-Hartman; Peter T Campbell; Graham Casey; Sergi Castellví-Bel; Andrew T Chan; Jenny Chang-Claude; Albert de la Chapelle; Jane C Figueiredo; Steven J Gallinger; Graham G Giles; Phyllis J Goodman; Andrea Gsur; Jochen Hampe; Heather Hampel; Michael Hoffmeister; Mark A Jenkins; Temitope O Keku; Sun-Seog Kweon; Susanna C Larsson; Loic Le Marchand; Christopher I Li; Li Li; Annika Lindblom; Vicente Martín; Roger L Milne; Victor Moreno; Hongmei Nan; Rami Nassir; Polly A Newcomb; Kenneth Offit; Paul DP Pharoah; Elizabeth A Platz; John D Potter; Lihong Qi; Gad Rennert; Lori C Sakoda; Clemens Schafmayer; Martha L Slattery; Linda Snetselaar; Jeanette Schenk; Stephen N Thibodeau; Cornelia M Ulrich; Bethany Van Guelpen; Sophia Harlid; Kala Visvanathan; Ludmila Vodickova; Hansong Wang; Emily White; Alicja Wolk; Michael O Woods; Anna H Wu; Wei Zheng; Bas Bueno-de-Mesquita; Marie-Christine Boutron-Ruault; David J Hughes; Paula Jakszyn; Tilman Kühn; Domenico Palli; Elio Riboli; Edward L Giovannucci; Barbara L Banbury; Stephen B Gruber; Ulrike Peters; Marc J Gunter; on behalf of GECCO, CORECT, and CCFR

doi:10.1093/ajcn/nqab003

Back

Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent: a Mendelian randomization study

Journal article

Open access

Peer reviewed

Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent: a Mendelian randomization study

Konstantinos K Tsilidis, Nikos Papadimitriou, Niki Dimou, Dipender Gill, Sarah J Lewis, Richard M Martin, Neil Murphy, Georgios Markozannes, Verena Zuber, Amanda J Cross, …

The American journal of clinical nutrition, Vol.113(6), pp.1490-1502

01/06/2021

DOI: https://doi.org/10.1093/ajcn/nqab003

PMID: 33740060

Abstract

colorectal cancer

genes

Mendelian randomization

nutrition

supplements

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.

Files and links (1)

url

https://doi.org/10.1093/ajcn/nqab003View

Published (Version of record) Open

Metrics

1 Record Views

See more details

Details

Title: Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent: a Mendelian randomization study
Creators - without role: Konstantinos K Tsilidis - Imperial College London
Nikos Papadimitriou - International Agency For Research On Cancer
Niki Dimou - International Agency For Research On Cancer
Dipender Gill - Imperial College London
Sarah J Lewis - University of Bristol
Richard M Martin - University of Bristol
Neil Murphy - International Agency For Research On Cancer
Georgios Markozannes - University of Ioannina
Verena Zuber - MRC Biostatistics Unit
Amanda J Cross - Imperial College London
Kimberley Burrows - University of Bristol
David S Lopez - The University of Texas Medical Branch at Galveston
Timothy J Key - University of Oxford
Ruth C Travis - University of Oxford
Aurora Perez-Cornago - University of Oxford
David J Hunter - University of Oxford
Fränzel JB van Duijnhoven - Wageningen University & Research
Demetrius Albanes - National Cancer Institute
Volker Arndt - German Cancer Research Center
Sonja I Berndt - National Cancer Institute
Stéphane Bézieau - Medical Genetics Service, University Hospital Center (CHU) Nantes, Nantes, France
D Timothy Bishop - University of Leeds
Juergen Boehm - University of Utah
Hermann Brenner - Heidelberg
Andrea Burnett-Hartman - Kaiser Permanente
Peter T Campbell - Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA, USA
Graham Casey - University of Virginia
Sergi Castellví-Bel - Universitat de Barcelona
Andrew T Chan - Harvard Medical School
Jenny Chang-Claude - Heidelberg
Albert de la Chapelle - The Ohio State University
Jane C Figueiredo - Cedars-Sinai Medical Center
Steven J Gallinger - University of Toronto
Graham G Giles - Cancer Council Victoria
Phyllis J Goodman - SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Andrea Gsur - Medical University of Vienna
Jochen Hampe - Department of Medicine I, University Hospital Dresden, Dresden University of Technology (TU Dresden), Dresden, Germany
Heather Hampel - The Ohio State University
Michael Hoffmeister - Heidelberg
Mark A Jenkins - University of Ioannina
Temitope O Keku - Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA
Sun-Seog Kweon - Chonnam National University
Susanna C Larsson - Karolinska Institutet
Loic Le Marchand - University of Hawaii System
Christopher I Li - Imperial College London
Li Li - Imperial College London
Annika Lindblom - Karolinska University Hospital
Vicente Martín - University of Bristol
Roger L Milne - Cancer Council Victoria
Victor Moreno - CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain
Hongmei Nan - University of Indianapolis
Rami Nassir - Netaji Subhas National Institute of Sports
Polly A Newcomb - Hutchinson
Kenneth Offit - Memorial Sloan Kettering Cancer Center
Paul DP Pharoah - University of Cambridge
Elizabeth A Platz - Bloomberg
John D Potter - Hutchinson
Lihong Qi - University of California, Davis
Gad Rennert - Carmel Medical Center
Lori C Sakoda - Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Clemens Schafmayer - Department of General Surgery, University Hospital Rostock, Rostock, Germany
Martha L Slattery - University of Utah
Linda Snetselaar - University of Iowa
Jeanette Schenk - SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Stephen N Thibodeau - Mayo Clinic
Cornelia M Ulrich - University of Utah
Bethany Van Guelpen - Umeå University
Sophia Harlid - Umeå University
Kala Visvanathan - Bloomberg
Ludmila Vodickova - Czech Academy of Sciences, Institute of Experimental Medicine
Hansong Wang - University of Hawaii System
Emily White - Hutchinson
Alicja Wolk - Karolinska Institutet
Michael O Woods - Memorial University of Newfoundland
Anna H Wu - Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Wei Zheng - Vanderbilt University School of Medicine
Bas Bueno-de-Mesquita - Formerly, Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands
Marie-Christine Boutron-Ruault - University of Paris-Saclay
David J Hughes - University College Dublin
Paula Jakszyn - Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology– Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain
Tilman Kühn - Heidelberg
Domenico Palli - Florence
Elio Riboli - Imperial College London
Edward L Giovannucci - Brigham and Women's Hospital
Barbara L Banbury - Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Stephen B Gruber - Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Ulrike Peters - Hutchinson
Marc J Gunter - Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France
on behalf of GECCO, CORECT, and CCFR
Publication Details: The American journal of clinical nutrition, Vol.113(6), pp.1490-1502
Publisher: Elsevier Inc
Identifiers: 9930918208331
Academic Unit: Umm Al Qura University
Language: English
Resource Type: Journal article