Nutrients (Apr 2019)
Association of Selenoprotein and Selenium Pathway Genotypes with Risk of Colorectal Cancer and Interaction with Selenium Status
- Veronika Fedirko,
- Mazda Jenab,
- Catherine Méplan,
- Jeb S. Jones,
- Wanzhe Zhu,
- Lutz Schomburg,
- Afshan Siddiq,
- Sandra Hybsier,
- Kim Overvad,
- Anne Tjønneland,
- Hanane Omichessan,
- Vittorio Perduca,
- Marie-Christine Boutron-Ruault,
- Tilman Kühn,
- Verena Katzke,
- Krasimira Aleksandrova,
- Antonia Trichopoulou,
- Anna Karakatsani,
- Anastasia Kotanidou,
- Rosario Tumino,
- Salvatore Panico,
- Giovanna Masala,
- Claudia Agnoli,
- Alessio Naccarati,
- Bas Bueno-de-Mesquita,
- Roel C.H. Vermeulen,
- Elisabete Weiderpass,
- Guri Skeie,
- Therese Haugdahl Nøst,
- Leila Lujan-Barroso,
- J. Ramón Quirós,
- José María Huerta,
- Miguel Rodríguez-Barranco,
- Aurelio Barricarte,
- Björn Gylling,
- Sophia Harlid,
- Kathryn E. Bradbury,
- Nick Wareham,
- Kay-Tee Khaw,
- Marc Gunter,
- Neil Murphy,
- Heinz Freisling,
- Kostas Tsilidis,
- Dagfinn Aune,
- Elio Riboli,
- John E. Hesketh,
- David J. Hughes
Affiliations
- Veronika Fedirko
- Department of Epidemiology, Rollins School of Public Health & Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA
- Mazda Jenab
- Section of Nutrition and Metabolism, International Agency for Research on Cancer, 69372 Lyon, France
- Catherine Méplan
- School of Biomedical Sciences, Newcastle University, Newcastle upon Tyne NE1 7RU, UK
- Jeb S. Jones
- Department of Epidemiology, Rollins School of Public Health & Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA
- Wanzhe Zhu
- Department of Epidemiology, Rollins School of Public Health & Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA
- Lutz Schomburg
- Institute for Experimental Endocrinology, University Medical School, D-13353 Berlin, Germany
- Afshan Siddiq
- Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London W2 1PG, UK
- Sandra Hybsier
- Institute for Experimental Endocrinology, University Medical School, D-13353 Berlin, Germany
- Kim Overvad
- Department of Public Health, Section for Epidemiology, Aarhus University, 8000 Aarhus, Denmark
- Anne Tjønneland
- Diet, Genes and Environment Unit, Danish Cancer Society Research Center, DK 2100 Copenhagen, Denmark
- Hanane Omichessan
- Faculty of Medicine, CESP, University of Paris-Sud, Faculty of Medicine UVSQ, INSERM, University of Paris-Saclay, 94805 Villejuif, France
- Vittorio Perduca
- Faculty of Medicine, CESP, University of Paris-Sud, Faculty of Medicine UVSQ, INSERM, University of Paris-Saclay, 94805 Villejuif, France
- Marie-Christine Boutron-Ruault
- Faculty of Medicine, CESP, University of Paris-Sud, Faculty of Medicine UVSQ, INSERM, University of Paris-Saclay, 94805 Villejuif, France
- Tilman Kühn
- Division of Cancer Epidemiology, German Cancer Research Centre (DKFZ), 69120 Heidelberg, Germany
- Verena Katzke
- Division of Cancer Epidemiology, German Cancer Research Centre (DKFZ), 69120 Heidelberg, Germany
- Krasimira Aleksandrova
- Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, 14558 Nuthetal, Germany
- Antonia Trichopoulou
- Hellenic Health Foundation, 115 27 Athens, Greece
- Anna Karakatsani
- Hellenic Health Foundation, 115 27 Athens, Greece
- Anastasia Kotanidou
- Hellenic Health Foundation, 115 27 Athens, Greece
- Rosario Tumino
- Cancer Registry and Histopathology Department, Civic M.P. Arezzo Hospital, 97100 Ragusa, Italy
- Salvatore Panico
- Department of Clinical Medicine and Surgery, Federico II University, 80138 Naples, Italy
- Giovanna Masala
- Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute—ISPO, 50141 Florence, Italy
- Claudia Agnoli
- Epidemiology and Prevention Unit, IRCCS Foundation National Cancer Institute, 20133 Milan, Italy
- Alessio Naccarati
- Molecular and Genetic Epidemiology Unit, Italian Institute for Genomic Medicine (IIGM) Torino, 10126 Torino, Italy
- Bas Bueno-de-Mesquita
- Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London W2 1PG, UK
- Roel C.H. Vermeulen
- Institute of Risk Assessment Sciences, Utrecht University, 3512 JE Utrecht, The Netherlands
- Elisabete Weiderpass
- Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, N-0304 Oslo, Norway
- Guri Skeie
- Department of Community Medicine, University of Tromsø, The Arctic University of Norway, 9019 Tromsø, Norway
- Therese Haugdahl Nøst
- Department of Community Medicine, University of Tromsø, The Arctic University of Norway, 9019 Tromsø, Norway
- Leila Lujan-Barroso
- Unit of Nutrition and Cancer, Catalan Institute of Oncology (ICO-IDIBELL), L’Hospitalet de Llobregat, 08908 Barcelona, Spain
- J. Ramón Quirós
- EPIC Asturias, Public Health Directorate, 33006 Oviedo, Asturias, Spain
- José María Huerta
- Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, 30008 Murcia, Spain
- Miguel Rodríguez-Barranco
- CIBER Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain
- Aurelio Barricarte
- CIBER Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain
- Björn Gylling
- Department of Medical Biosciences, Pathology, Umea University, 901 87 Umea, Sweden
- Sophia Harlid
- Department of Radiation Sciences, Oncology, Umea University, 901 87 Umea, Sweden
- Kathryn E. Bradbury
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK
- Nick Wareham
- MRC Epidemiology Unit, University of Cambridge, CB2 0QQ Cambridge, UK
- Kay-Tee Khaw
- School of Clinical Medicine, University of Cambridge, Clinical Gerontology Unit, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK
- Marc Gunter
- Section of Nutrition and Metabolism, International Agency for Research on Cancer, 69372 Lyon, France
- Neil Murphy
- Section of Nutrition and Metabolism, International Agency for Research on Cancer, 69372 Lyon, France
- Heinz Freisling
- Section of Nutrition and Metabolism, International Agency for Research on Cancer, 69372 Lyon, France
- Kostas Tsilidis
- Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London W2 1PG, UK
- Dagfinn Aune
- Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London W2 1PG, UK
- Elio Riboli
- Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London W2 1PG, UK
- John E. Hesketh
- School of Biomedical Sciences, Newcastle University, Newcastle upon Tyne NE1 7RU, UK
- David J. Hughes
- Cancer Biology and Therapeutics Group, UCD Conway Institute, School of Biomolecular and Biomedical Science, University College Dublin, D04 V1W8 Dublin, Ireland
- DOI
- https://doi.org/10.3390/nu11040935
- Journal volume & issue
-
Vol. 11,
no. 4
p. 935
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.
Keywords
- selenium
- selenium status
- selenoprotein gene variation
- selenium pathway
- colorectal neoplasms
- selenoprotein P
- prospective cohort
- colorectal cancer risk
- genetic epidemiology
- biomarkers