About this item:

84 Views | 87 Downloads

Author Notes:

Correspondence: david.hughes@ucd.ie; Tel.: +353-1-716-6988

Jeb Jones ORCID: https://orcid.org/0000-0001-9165-1658

Conceptualization, D.J.H., V.F., C.M., J.E.H., L.S., M.J. and E.R.; Data curation, D.J.H., J.E.H., V.F., L.S. and M.J.; Formal analysis, V.F., D.J.H., J.S.J., W.Z., C.M. and M.J.; Funding acquisition, D.J.H., V.F., J.E.H., C.M., L.S. and M.J.

Investigation, D.J.H., V.F., C.M., J.E.H., L.S., S.H. (Sandra Hybsier), A.S. and M.J.; Methodology, V.F., D.J.H., J.E.H., C.M., M.J., L.S. and E.R.; Project administration, D.J.H., V.F., C.M., J.E.H. and M.J.

Resources, D.J.H., V.F., C.M., J.E.H., M.J., and all other EPIC co-authors (K.O., A.T. (Anne Tjønneland), H.O., V.P., M.-C.B.-R.,T.K., V.K., K.A., A.Tr., A.K. (Anna Karakatsani), A.K. (Anastasia Kotanidou), R.T., S.P., G.M., C.A., A.N., B.B.-d.-M., R.C.H.V., E.W., G.S., T.H.N., L.L.-B., J.R.Q., J.M.H., M.R.-B., A.B., B.G., S.H. (Sophia Harlid), K.E.B., N.W., K.-T.K., M.G., N.M., H.F., K.T., D.A., and E.R.); Software, V.F., D.J.H., A.S., J.S.J., W.Z., L.S. and M.J.; Supervision, D.J.H., V.F., L.S. and M.J.; Validation, D.J.H., V.F., C.M., A.S., S.H. (Sandra Hybsier) and L.S.; Writing—original draft, D.J.H., V.F., M.J., C.M., and J.E.H.; Writing—review and editing, all other EPIC co-authors (K.O., A.T. (Anne Tjønneland), H.O., V.P., M.-C.B.-R.,T.K., V.K., K.A., A.T. (Antonia Trichopoulou), A.K. (Anna Karakatsani), A.K. (Anastasia Kotanidou), R.T., S.P., G.M., C.A., A.N., B.B.-d.-M., R.C.H.V., E.W., G.S., T.H.N., L.L.-B., J.R.Q., J.M.H., M.R.-B., A.B., B.G., S.H. (Sophia Harlid), K.E.B., N.W., K.-T.K., M.G., N.M., H.F., K.T., D.A. and E.R.) reviewed and approved the manuscript and commented on the analysis and interpretation of the findings.

The lead authors (D.J.H., V.F., C.M., J.E.H. and M.J.) affirm that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.

We thank all the members of EPIC for their work on the EPIC cohort study.

The authors declare no competing interests.

Subjects:

Research Funding:

Funding for this study was provided by the Health Research Board of Ireland health research awards HRA_PHS/2013/397 and HRA_PHS/2015/1142 (principal investigator: D.J.H.).

The EPIC study was supported by “Europe Against Cancer” Programme of the European Commission (SANCO); Ligue contre le Cancer; Institut Gustave Roussy; Mutuelle Générale de l’Education Nationale; Institut National de la Santé et de la Recherche Médicale (INSERM); German Cancer Aid; German Cancer Research Center; German Federal Ministry of Education and Research; Danish Cancer Society; Health Research Fund (FIS) of the Spanish Ministry of Health; the CIBER en Epidemiología y Salud Pública (CIBERESP), Spain; ISCIII RETIC (RD06/0020); Spanish Regional Governments of Andalusia, Asturias, Basque Country, Murcia (No 6236) and Navarra and the Catalan Institute of Oncology; Cancer Research UK; Medical Research Council, UK; the Hellenic Health Foundation; Italian Association for Research on Cancer; Italian National Research Council; Compagnia di San Paolo; Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (ZorgOnderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Swedish Cancer Society; Swedish Scientific Council; Regional Governments of Skane and Vasterbotten, Sweden; and Nordforsk center of excellence programme HELGA.

L.S. was supported by Deutsche Forschungsgemeinschaft (DFG Research Unit 2558 TraceAge, Scho 849/6-1).

D.P. was supported by the Associazione Italiana per la Ricercasul Cancro-AIRC-Italy.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Nutrition & Dietetics
  • selenium
  • selenium status
  • selenoprotein gene variation
  • selenium pathway
  • colorectal neoplasms
  • selenoprotein P
  • prospective cohort
  • colorectal cancer risk
  • genetic epidemiology
  • biomarkers
  • FRIZZLED-RELATED PROTEIN
  • GENETIC-VARIANTS
  • CROHNS-DISEASE
  • SUSCEPTIBILITY
  • POLYMORPHISM
  • METAANALYSIS
  • MEGALIN
  • HEALTH
  • ARCHITECTURE
  • BIOMARKERS

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

Show all authors Show less authors

Tools:

Proceedings Title:

Nutrients

Publisher:

Conference Place:

Switzerland

Volume/Issue:

Volume 11 | Issue 4

Publication Date:

Type of Work:

Conference | Final Publisher PDF

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.

Copyright information:

© 2019 by the authors.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
Export to EndNote