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

Title: Association of Selenoprotein and Selenium Pathway Genotypes with Risk of Colorectal Cancer and Interaction with Selenium Status
Authors: Fedirko, VeronikaJenab, MazdaMéplan, CatherineHughes, David J.et al.
Permanent link: http://hdl.handle.net/10197/10809
Date: 25-Apr-2019
Online since: 2019-07-01T09:25:54Z
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.
Funding Details: European Commission
Health Research Board
Type of material: Journal Article
Publisher: MDPI
Journal: Nutrients
Volume: 11
Issue: 4
Start page: 1
End page: 14
Copyright (published version): 2019 the Authors
Keywords: SeleniumSelenium statusSelenoprotein gene variationSelenium pathwayColorectal neoplasmsSelenoprotein PProspective cohortColorectal cancer riskGenetic epidemiologyBiomarkers
DOI: 10.3390/nu11040935
Language: en
Status of Item: Peer reviewed
ISBN: 9781138027312
Appears in Collections:Biomolecular and Biomedical Science Research Collection

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