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

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  • Veronika Fedirko, Department of Epidemiology, Rollins School of Public Health & Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA. veronika.fedirko@emory.edu., USA
  • Mazda Jenab, Nutritional Epidemiology Group, Nutrition and Metabolism Section, International Agency for Research on Cancer (IARC-WHO), 69372 Lyon, France. jenabm@iarc.fr., Frankrig
  • Catherine Méplan, School of Biomedical Sciences, Newcastle University, Newcastle upon Tyne NE1 7RU, UK. Catherine.Meplan@newcastle.ac.uk., Storbritannien
  • Jeb S Jones, Department of Epidemiology, Rollins School of Public Health & Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA. jeb.jones@emory.edu., USA
  • Wanzhe Zhu, Department of Epidemiology, Rollins School of Public Health & Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA. WZHU4@emory.edu., USA
  • Lutz Schomburg, Institute for Experimental Endocrinology, University Medical School, D-13353 Berlin, Germany. lutz.schomburg@charite.de., Tyskland
  • Afshan Siddiq, Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London W2 1PG, UK. afshan.siddiq@genomicsengland.co.uk., Storbritannien
  • Sandra Hybsier, Institute for Experimental Endocrinology, University Medical School, D-13353 Berlin, Germany. sandra.hybsier@charite.de., Tyskland
  • Kim Overvad
  • Anne Tjønneland, Diet, Genes and Environment Unit, Danish Cancer Society Research Center, DK 2100 Copenhagen, Denmark. annet@cancer.dk., Danmark
  • Hanane Omichessan, Centre for Research in Epidemiology and Population Health (CESP), F-94805 Gustave Roussy, Villejuif, France. HANANE.OMICHESSAN@gustaveroussy.fr., Frankrig
  • Vittorio Perduca, Laboratory of Applied Mathematics, MAP5 (UMR CNRS 8145), University of Paris Descartes, 75270 Paris, France. vittorio.perduca@gmail.com., Frankrig
  • Marie-Christine Boutron-Ruault, Centre for Research in Epidemiology and Population Health (CESP), F-94805 Gustave Roussy, Villejuif, France. boutron@igr.fr., Frankrig
  • Tilman Kühn, Division of Cancer Epidemiology, German Cancer Research Centre (DKFZ), 69120 Heidelberg, Germany. t.kuehn@dkfz-Heidelberg.de., Tyskland
  • Verena Katzke, Division of Cancer Epidemiology, German Cancer Research Centre (DKFZ), 69120 Heidelberg, Germany. v.katzke@dkfz-Heidelberg.de., Tyskland
  • Krasimira Aleksandrova, Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, 14558 Nuthetal, Germany. Krasimira.Aleksandrova@dife.de., Tyskland
  • Antonia Trichopoulou, Hellenic Health Foundation, 115 27 Athens, Greece. atrichopoulou@hhf-greece.gr., Grækenland
  • Anna Karakatsani, 2nd Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, "ATTIKON" University Hospital, 106 79 Haidari, Greece. a.karakatsani@hhf-greece.gr., Grækenland
  • Anastasia Kotanidou, 1st Department of Critical Care Medicine and Pulmonary Services, University of Athens Medical School, Evangelismos Hospital, 106 76 Athens, Greece. a.kotanidou@hhf-greece.gr., Grækenland
  • Rosario Tumino, Cancer Registry and Histopathology Department, Civic M.P. Arezzo Hospital, 97100 Ragusa, Italy. rtumino@tin.it., Italien
  • Salvatore Panico, Department of Clinical Medicine and Surgery, Federico II University, 80138 Naples, Italy. spanico@unina.it., Italien
  • Giovanna Masala, Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, 50141 Florence, Italy. g.masala@ispo.toscana.it., Italien
  • Claudia Agnoli, Epidemiology and Prevention Unit, IRCCS Foundation National Cancer Institute, 20133 Milan, Italy. claudia.agnoli@istitutotumori.mi.it., Italien
  • Alessio Naccarati, Molecular and Genetic Epidemiology Unit, Italian Institute for Genomic Medicine (IIGM) Torino, 10126 Torino, Italy. alessio.naccarati@hugef-torino.org., Italien
  • Bas Bueno-de-Mesquita, Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia. bas.bueno.de.mesquita@rivm.nl., Holland
  • Roel C H Vermeulen, Institute of Risk Assessment Sciences, Utrecht University, 3512 JE Utrecht, The Netherlands. R.C.H.Vermeulen@uu.nl., Holland
  • Elisabete Weiderpass, Department of Community Medicine, University of Tromsø, The Arctic University of Norway, 9019 Tromsø, Norway. WeiderpassE@iarc.fr., Frankrig
  • Guri Skeie, Department of Community Medicine, University of Tromsø, The Arctic University of Norway, 9019 Tromsø, Norway. Guri.Skeie@ism.uit.no., Norge
  • Therese Haugdahl Nøst, Department of Community Medicine, University of Tromsø, The Arctic University of Norway, 9019 Tromsø, Norway. therese.h.nost@uit.no., Norge
  • Leila Lujan-Barroso, Unit of Nutrition and Cancer, Catalan Institute of Oncology (ICO-IDIBELL), L'Hospitalet de Llobregat, 08908 Barcelona, Spain. llujan@iconcologia.net., Spanien
  • J Ramón Quirós, EPIC Asturias, Public Health Directorate, Asturias, 33006 Oviedo, Spain. joseramon.quirosgarcia@asturias.org., Spanien
  • José María Huerta, CIBER Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain. jmhuerta.carm@gmail.com., Spanien
  • Miguel Rodríguez-Barranco, Andalucia School of Public Health, Institute for Biosanitary Research, University Hospital of Granada, University of Granada, 18011 Granada, Spain. miguel.rodriguez.barranco.easp@juntadeandalucia.es., Spanien
  • Aurelio Barricarte, Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain. aurelio.barricarte.gurrea@cfnavarra.es., Spanien
  • Björn Gylling, Department of Medical Biosciences, Pathology, Umea University, 901 87 Umea, Sweden. bjorn.gylling@umu.se., Sverige
  • Sophia Harlid, Department of Radiation Sciences, Oncology, Umea University, 901 87 Umea, Sweden. sophia.harlid@umu.se., Sverige
  • Kathryn E Bradbury, Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK. kathryn.bradbury@ceu.ox.ac.uk., Storbritannien
  • Nick Wareham, MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK. nick.wareham@mrc-epid.cam.ac.uk., Storbritannien
  • Kay-Tee Khaw, School of Clinical Medicine, University of Cambridge, Clinical Gerontology Unit, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK. kk101@medschl.cam.ac.uk., Storbritannien
  • Marc Gunter, Nutritional Epidemiology Group, Nutrition and Metabolism Section, International Agency for Research on Cancer (IARC-WHO), 69372 Lyon, France. GunterM@iarc.fr., Frankrig
  • Neil Murphy, Nutritional Epidemiology Group, Nutrition and Metabolism Section, International Agency for Research on Cancer (IARC-WHO), 69372 Lyon, France. MurphyN@iarc.fr., Frankrig
  • Heinz Freisling, Nutritional Methodology and Biostatistics Group, Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), 150, Cours Albert Thomas, 69372, Lyon Cedex 08, France. freislingh@iarc.fr., Frankrig
  • Kostas Tsilidis, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, 45110 Ioannina, Greece. ktsilidis@gmail.com., Grækenland
  • Dagfinn Aune, Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, 0372 Oslo, Norway. d.aune@imperial.ac.uk., Norge
  • Elio Riboli, Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London W2 1PG, UK. e.riboli@imperial.ac.uk., Storbritannien
  • John E Hesketh, School of Biomedical Sciences, Newcastle University, Newcastle upon Tyne NE1 7RU, UK. j.hesketh@rgu.ac.uk., Storbritannien
  • David J Hughes, 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., Irland

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.

OriginalsprogEngelsk
TidsskriftNutrients
Vol/bind11
Nummer4
Sider (fra-til)935
Antal sider19
ISSN2072-6643
DOI
StatusUdgivet - 25 apr. 2019

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