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Association of selenoprotein and selenium pathway genotypes with risk of colorectal cancer and interaction with selenium status.

Fedirko, Veronika; Jenab, Mazda; M�plan, Catherine; Jones, Jeb S.; Zhu, Wanzhe; Schomburg, Lutz; Siddiq, Afshan; Hybsier, Sandra; Overvad, Kim; Tj�nneland, Anne; Omichessan, Hanane; Perduca, Vittorio; Boutron-Ruault, Marie-Christine; K�hn, Tilman; Katzke, Verena; Aleksandrova, Krasimira; Trichopoulou, Antonia; Karakatsani, Anna; Kotanidou, Anastasia; Tumino, Rosario; Panico, Salvatore; Masala, Giovanna; Agnoli, Claudia; Naccarati, Alessio; Bueno-de-Mesquita, Bas; Vermeulen, Roel C.H.; Weiderpass, Elisabete; Skeie, Guri; N�st, Therese Haugdahl; Lujan-Barroso, Leila; Quir�s, J. Ram�n; Huerta, Jos� Mar�a; Rodr�guez-Barranco, Miguel; Barricarte, Aurelio; Gylling, Bj�rn; Harlid, Sophia; Bradbury, Kathryn E.; Wareham, Nick; Khaw, Kay-Tee; Gunter, Marc; Murphy, Neil; Freisling, Heinz; Tsilidis, Kostas; Aune, Dagfinn; Riboli, Elio; Hesketh, John E.; Hughes, David J.


Veronika Fedirko

Mazda Jenab

Catherine M�plan

Jeb S. Jones

Wanzhe Zhu

Lutz Schomburg

Afshan Siddiq

Sandra Hybsier

Kim Overvad

Anne Tj�nneland

Hanane Omichessan

Vittorio Perduca

Marie-Christine Boutron-Ruault

Tilman K�hn

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 N�st

Leila Lujan-Barroso

J. Ram�n Quir�s

Jos� Mar�a Huerta

Miguel Rodr�guez-Barranco

Aurelio Barricarte

Bj�rn 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


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.


FEDIRKO, V., JENAB, M., MÉPLAN, C., 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:

Journal Article Type Article
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
Keywords Selenium; Selenium status; Selenoprotein gene variation; Selenium pathway; Colorectal neoplasms; Selenoprotein P; Prospective cohort; Colorectal cancer risk; Genetic epidemiology; Biomarkers
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