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

Year: 2019

Type: article

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.

Source: Nutrients

DOI: 10.3390/nu11040935

Authors: 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

Institutions: Emory University, Winship Cancer Institute, Centre international de recherche sur le cancer, Newcastle University, Imperial College London, Aarhus University, Danish Cancer Society, Université Paris-Sud, Inserm, Université de Versailles Saint-Quentin-en-Yvelines, Université Paris-Saclay, Centre de recherche en Epidémiologie et Santé des Populations, Centre National de la Recherche Scientifique, Mathématiques Appliquées à Paris 5, Université Paris Descartes, German Cancer Research Center, German Institute of Human Nutrition, Hellenic Health Foundation, National and Kapodistrian University of Athens, University General Hospital Attikon, Evangelismos Hospital, Federico II University Hospital, University of Naples Federico II, Istituto per lo Studio e la Prevenzione Oncologica, Fondazione IRCCS Istituto Nazionale dei Tumori, Italian institute for Genomic Medicine, University Medical Center Utrecht, University of Malaya, National Institute for Public Health and the Environment, Utrecht University, University of Helsinki, Karolinska Institutet, Cancer Registry of Norway, Folkhälsans Forskningscentrum, UiT The Arctic University of Norway, Institut d'Investigació Biomédica de Bellvitge, Institut Català d'Oncologia, Instituto Murciano de Investigación Biosanitaria, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Universidad de Granada, Andalusian School of Public Health, Instituto de Salud Pública de Navarra, Navarre Institute of Health Research, Umeå University, University of Oxford, University of Cambridge, MRC Epidemiology Unit, Addenbrooke's Hospital, University of Ioannina, Oslo University Hospital, Oslo Nye Høyskole, University College Dublin

Language: English

Topic: Selenium in Biological Systems

Subfield: Nutrition and Dietetics

Field: Nursing

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,026

OpenAlex ID: W2941462732