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Association of Selenoprotein and Selenium Pathway Genotypes with Risk of Colorectal Cancer and Interaction with Selenium Status

Fedirko V 1 , Jenab M 2 , Méplan C 3 , Jones JS 4 , Zhu W 5 , Schomburg L 6 Show all authors , Siddiq A 7 , Hybsier S 8 , Overvad K 9 , Tjønneland A 10 , Omichessan H 11 , Perduca V 12 , Boutron-Ruault MC 13 , Kühn T 14 , Katzke V 15 , Aleksandrova K 16 , Trichopoulou A 17 , Karakatsani A 18 , Kotanidou A 19 , Tumino R 20 , Panico S 21 , Masala G 22 , Agnoli C 23 , Naccarati A 24 , Bueno-de-Mesquita B 25 , Vermeulen RCH 26 , Weiderpass E 27 , Skeie G 28 , Nøst TH 29 , Lujan-Barroso L 30 , Quirós JR 31 , Huerta JM 32 , Rodríguez-Barranco M 33 , Barricarte A 34 , Gylling B 35 , Harlid S 36 , Bradbury KE 37 , Wareham N 38 , Khaw KT 39 , Gunter M 40 , Murphy N 41 , Freisling H 42 , Tsilidis K 43 , Aune D 44 , Riboli E 45 , Hesketh JE 46 , Hughes DJ 47

Affiliations 

  • 1 Department of Epidemiology, Rollins School of Public Health & Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA. veronika.fedirko@emory.edu
  • 2 Section of Nutrition and Metabolism, International Agency for Research on Cancer, 69372 Lyon, France. jenabm@iarc.fr
  • 3 School of Biomedical Sciences, Newcastle University, Newcastle upon Tyne NE1 7RU, UK. Catherine.Meplan@newcastle.ac.uk
  • 4 Department of Epidemiology, Rollins School of Public Health & Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA. jeb.jones@emory.edu
  • 5 Department of Epidemiology, Rollins School of Public Health & Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA. WZHU4@emory.edu
  • 6 Institute for Experimental Endocrinology, University Medical School, D-13353 Berlin, Germany. lutz.schomburg@charite.de
  • 7 Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London W2 1PG, UK. afshan.siddiq@genomicsengland.co.uk
  • 8 Institute for Experimental Endocrinology, University Medical School, D-13353 Berlin, Germany. sandra.hybsier@charite.de
  • 9 Department of Public Health, Section for Epidemiology, Aarhus University, 8000 Aarhus, Denmark. ko@dce.au.dk
  • 10 Diet, Genes and Environment Unit, Danish Cancer Society Research Center, DK 2100 Copenhagen, Denmark. annet@cancer.dk
  • 11 Faculty of Medicine, CESP, University of Paris-Sud, Faculty of Medicine UVSQ, INSERM, University of Paris-Saclay, 94805 Villejuif, France. HANANE.OMICHESSAN@gustaveroussy.fr
  • 12 Faculty of Medicine, CESP, University of Paris-Sud, Faculty of Medicine UVSQ, INSERM, University of Paris-Saclay, 94805 Villejuif, France. vittorio.perduca@gmail.com
  • 13 Faculty of Medicine, CESP, University of Paris-Sud, Faculty of Medicine UVSQ, INSERM, University of Paris-Saclay, 94805 Villejuif, France. boutron@igr.fr
  • 14 Division of Cancer Epidemiology, German Cancer Research Centre (DKFZ), 69120 Heidelberg, Germany. t.kuehn@dkfz-Heidelberg.de
  • 15 Division of Cancer Epidemiology, German Cancer Research Centre (DKFZ), 69120 Heidelberg, Germany. v.katzke@dkfz-Heidelberg.de
  • 16 Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, 14558 Nuthetal, Germany. Krasimira.Aleksandrova@dife.de
  • 17 Hellenic Health Foundation, 115 27 Athens, Greece. atrichopoulou@hhf-greece.gr
  • 18 Hellenic Health Foundation, 115 27 Athens, Greece. a.karakatsani@hhf-greece.gr
  • 19 Hellenic Health Foundation, 115 27 Athens, Greece. a.kotanidou@hhf-greece.gr
  • 20 Cancer Registry and Histopathology Department, Civic M.P. Arezzo Hospital, 97100 Ragusa, Italy. rtumino@tin.it
  • 21 Department of Clinical Medicine and Surgery, Federico II University, 80138 Naples, Italy. spanico@unina.it
  • 22 Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, 50141 Florence, Italy. g.masala@ispo.toscana.it
  • 23 Epidemiology and Prevention Unit, IRCCS Foundation National Cancer Institute, 20133 Milan, Italy. claudia.agnoli@istitutotumori.mi.it
  • 24 Molecular and Genetic Epidemiology Unit, Italian Institute for Genomic Medicine (IIGM) Torino, 10126 Torino, Italy. alessio.naccarati@hugef-torino.org
  • 25 Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London W2 1PG, UK. bas.bueno.de.mesquita@rivm.nl
  • 26 Institute of Risk Assessment Sciences, Utrecht University, 3512 JE Utrecht, The Netherlands. R.C.H.Vermeulen@uu.nl
  • 27 Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, N-0304 Oslo, Norway. WeiderpassE@iarc.fr
  • 28 Department of Community Medicine, University of Tromsø, The Arctic University of Norway, 9019 Tromsø, Norway. Guri.Skeie@ism.uit.no
  • 29 Department of Community Medicine, University of Tromsø, The Arctic University of Norway, 9019 Tromsø, Norway. therese.h.nost@uit.no
  • 30 Unit of Nutrition and Cancer, Catalan Institute of Oncology (ICO-IDIBELL), L'Hospitalet de Llobregat, 08908 Barcelona, Spain. llujan@iconcologia.net
  • 31 EPIC Asturias, Public Health Directorate, 33006 Oviedo, Asturias, Spain. joseramon.quirosgarcia@asturias.org
  • 32 Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, 30008 Murcia, Spain. jmhuerta.carm@gmail.com
  • 33 CIBER Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain. miguel.rodriguez.barranco.easp@juntadeandalucia.es
  • 34 CIBER Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain. aurelio.barricarte.gurrea@cfnavarra.es
  • 35 Department of Medical Biosciences, Pathology, Umea University, 901 87 Umea, Sweden. bjorn.gylling@umu.se
  • 36 Department of Radiation Sciences, Oncology, Umea University, 901 87 Umea, Sweden. sophia.harlid@umu.se
  • 37 Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK. kathryn.bradbury@ceu.ox.ac.uk
  • 38 MRC Epidemiology Unit, University of Cambridge, CB2 0QQ Cambridge, UK. nick.wareham@mrc-epid.cam.ac.uk
  • 39 School of Clinical Medicine, University of Cambridge, Clinical Gerontology Unit, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK. kk101@medschl.cam.ac.uk
  • 40 Section of Nutrition and Metabolism, International Agency for Research on Cancer, 69372 Lyon, France. GunterM@iarc.fr
  • 41 Section of Nutrition and Metabolism, International Agency for Research on Cancer, 69372 Lyon, France. MurphyN@iarc.fr
  • 42 Section of Nutrition and Metabolism, International Agency for Research on Cancer, 69372 Lyon, France. FreislingH@iarc.fr
  • 43 Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London W2 1PG, UK. ktsilidis@gmail.com
  • 44 Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London W2 1PG, UK. d.aune@imperial.ac.uk
  • 45 Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London W2 1PG, UK. e.riboli@imperial.ac.uk
  • 46 School of Biomedical Sciences, Newcastle University, Newcastle upon Tyne NE1 7RU, UK. j.hesketh@rgu.ac.uk
  • 47 Cancer Biology and Therapeutics Group, UCD Conway Institute, School of Biomolecular and Biomedical Science, University College Dublin, D04 V1W8 Dublin, Ireland. david.hughes@ucd.ie
Nutrients, 2019 Apr 25;11(4).
PMID: 31027226 DOI: 10.3390/nu11040935

Abstract

Selenoprotein genetic variations and suboptimal selenium (Se) levels may contribute to the risk of colorectal cancer (CRC) development. We examined the association between CRC risk and genotype for single nucleotide polymorphisms (SNPs) in selenoprotein and Se metabolic pathway genes. Illumina Goldengate assays were designed and resulted in the genotyping of 1040 variants in 154 genes from 1420 cases and 1421 controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Multivariable logistic regression revealed an association of 144 individual SNPs from 63 Se pathway genes with CRC risk. However, regarding the selenoprotein genes, only TXNRD1 rs11111979 retained borderline statistical significance after adjustment for correlated tests (PACT = 0.10; PACT significance threshold was P < 0.1). SNPs in Wingless/Integrated (Wnt) and Transforming growth factor (TGF) beta-signaling genes (FRZB, SMAD3, SMAD7) from pathways affected by Se intake were also associated with CRC risk after multiple testing adjustments. Interactions with Se status (using existing serum Se and Selenoprotein P data) were tested at the SNP, gene, and pathway levels. Pathway analyses using the modified Adaptive Rank Truncated Product method suggested that genes and gene x Se status interactions in antioxidant, apoptosis, and TGF-beta signaling pathways may be associated with CRC risk. This study suggests that SNPs in the Se pathway alone or in combination with suboptimal Se status may contribute to CRC development.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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