@article{2987724,
    title = "Association of selenoprotein and selenium pathway genotypes with risk of colorectal cancer and interaction with selenium status",
    author = "Fedirko, V. and Jenab, M. and Méplan, C. and Jones, J.S. and Zhu, W. and Schomburg, L. and Siddiq, A. and Hybsier, S. and Overvad, K. and Tjønneland, A. and Omichessan, H. and Perduca, V. and Boutron-Ruault, M.-C. and Kühn, T. and Katzke, V. and Aleksandrova, K. and Trichopoulou, A. and Karakatsani, A. and Kotanidou, A. and Tumino, R. and Panico, S. and Masala, G. and Agnoli, C. and Naccarati, A. and Bueno-De-Mesquita, B. and Vermeulen, R.C.H. and Weiderpass, E. and Skeie, G. and Nøst, T.H. and Lujan-Barroso, L. and Quirós, J.R. and Huerta, J.M. and Rodríguez-Barranco, M. and Barricarte, A. and Gylling, B. and Harlid, S. and Bradbury, K.E. and Wareham, N. and Khaw, K.-T. and Gunter, M. and Murphy, N. and Freisling, H. and Tsilidis, K. and Aune, D. and Riboli, E. and Hesketh, J.E. and Hughes, D.J.",
    journal = "Nutrient Cycling in Agroecosystems",
    year = "2019",
    volume = "11",
    number = "4",
    publisher = "MDPI AG",
    issn = "1385-1314",
    doi = "10.3390/NU11040935",
    keywords = "selenium;  selenoprotein;  Smad3 protein;  Smad7 protein;  transforming growth factor beta;  Wnt protein;  selenium;  selenoprotein, adult;  aged;  anthropometric parameters;  antioxidant activity;  apoptosis;  Article;  bioassay;  blood sampling;  cancer hormone therapy;  cancer incidence;  cancer risk;  clinical trial;  cohort analysis;  colorectal cancer;  controlled study;  DNA extraction;  DNA repair;  environmental factor;  enzyme linked immunosorbent assay;  female;  follow up;  FRZB gene;  gene;  gene interaction;  genetic selection;  genetic variation;  genome-wide association study;  genotype;  human;  illumina goldengate assay;  major clinical study;  male;  middle aged;  multicenter study;  physical activity;  protein metabolism;  protein protein interaction;  questionnaire;  selenium pathway;  selenium status assay;  signal transduction;  single nucleotide polymorphism;  TGF beta signaling;  Wnt signaling;  colorectal tumor;  gene expression regulation;  genetic predisposition;  genetics;  metabolism;  nutritional status;  prospective study, Adult;  Aged;  Cohort Studies;  Colorectal Neoplasms;  Female;  Gene Expression Regulation;  Genetic Predisposition to Disease;  Genotype;  Humans;  Male;  Middle Aged;  Nutritional Status;  Polymorphism, Single Nucleotide;  Prospective Studies;  Selenium;  Selenoproteins",
    abstract = "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. © 2019 by the authors. Licensee MDPI, Basel, Switzerland."
}