Veronika Fedirko
Association of selenoprotein and selenium pathway genotypes with risk of colorectal cancer and interaction with selenium status.
Authors
Mazda Jenab
Catherine
Jeb S. Jones
Wanzhe Zhu
Lutz Schomburg
Afshan Siddiq
Sandra Hybsier
Kim Overvad
Anne
Hanane Omichessan
Vittorio Perduca
Marie-Christine Boutron-Ruault
Tilman
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
Leila Lujan-Barroso
Huerta
Miguel
Aurelio Barricarte
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
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.
Citation
FEDIRKO, V., JENAB, M., MÉPLAN, C., et.al. 2019. Association of selenoprotein and selenium pathway genotypes with risk of colorectal cancer and interaction with selenium status. Nutrients [online], 11(4), article ID 935. Available from: https://doi.org/10.3390/nu11040935
Journal Article Type | Article |
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Acceptance Date | Apr 22, 2019 |
Online Publication Date | Apr 25, 2019 |
Publication Date | Apr 30, 2019 |
Deposit Date | May 3, 2019 |
Publicly Available Date | May 6, 2019 |
Journal | Nutrients |
Electronic ISSN | 2072-6643 |
Publisher | MDPI |
Peer Reviewed | Peer Reviewed |
Volume | 11 |
Issue | 4 |
Article Number | 935 |
DOI | https://doi.org/10.3390/nu11040935 |
Keywords | Selenium; Selenium status; Selenoprotein gene variation; Selenium pathway; Colorectal neoplasms; Selenoprotein P; Prospective cohort; Colorectal cancer risk; Genetic epidemiology; Biomarkers |
Public URL | https://rgu-repository.worktribe.com/output/240451 |
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https://creativecommons.org/licenses/by/4.0/