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

Veronika Fedirko , Mazda Jenab (1) , Catherine Méplan , Jeb Jones , Wanzhe Zhu , Lutz Schomburg (2) , Afshan Siddiq (3) , Sandra Hybsier , Kim Overvad (4) , Anne Tjønneland , Hanane Omichessan , Vittorio Perduca (5) , Marie-Christine Boutron-Ruault (6) , Tilman Kühn , Verena Katzke (7) , Krasimira Aleksandrova (8) , Antonia Trichopoulou (9) , Anna Karakatsani , Anastasia Kotanidou , Rosario Tumino (10) , Salvatore Panico (11) , Giovanna Masala (12) , Claudia Agnoli (13) , Alessio Naccarati , Bas Bueno-De-Mesquita (14) , Roel C.H. Vermeulen , Elisabete Weiderpass (15) , Guri Skeie (16) , Therese Haugdahl Nøst , Leila Lujan-Barroso (17) , J. Ramón Quirós , José María Huerta (18) , Miguel Rodríguez-Barranco , Aurelio Barricarte (19) , Björn Gylling , Sophia Harlid , Kathryn Bradbury , Nick Wareham (20) , Kay-Tee Khaw (21) , Marc Gunter (22) , Neil Murphy , Heinz Freisling , Kostas Tsilidis (23) , Dagfinn Aune , Elio Riboli (24) , John Hesketh (25) , David Hughes

1 IACR - International Agency for Cancer Research
2 Experimental Endocrinology
3 Imperial College London
4 Department of Clinical Epidemiology
5 MAP5 - UMR 8145 - Mathématiques Appliquées Paris 5
6 E3N - Nutrition, hormones et cancer: épidémiologie et prévention
7 Division of Cancer Epidemiology
8 Department of Epidemiology
9 Department of Hygiene, Epidemiology and Medical Statistics
10 Cancer Registry and Histopathology Unit
11 Department of Clinical and Experimental Medicine
12 ISPO - Molecular and Nutritional Epidemiology Unit
13 IRCCS Istituto Nazionale dei Tumori [Milano]
14 RIVM - National Institute for Public Health and the Environment [Bilthoven]
15 MEB - Department of Medical Epidemiology and Biostatistics
16 Institute of Community Medicine
17 IDIBELL - Institut d'Investigació Biomèdica de Bellvitge = Bellvitge Biomedical Research Institute
18 CIBERESP - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública = Consortium for Biomedical Research of Epidemiology and Public Health
19 Danish Cancer Society Research Center
20 MRC epidemiology Unit
21 Clinical Gerontology Unit
22 Nutrition and Metabolism Section
23 University of Oxford
24 Department of Epidemiology and Biostatistics
25 School of Cellular and Molecular Biosciences

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

Mots clés: selenium; selenium status; selenoprotein gene variation; selenium pathway; colorectal neoplasms; selenoproteinP; prospectivecohort; colorectalcancerrisk; geneticepidemiology; biomarkers

Domaines: Génétique humaine; Alimentation et Nutrition; Cancer; Génétique des populations [q-bio.PE]; Hépatologie et Gastroentérologie; Santé publique et épidémiologie

Veronika Fedirko, Mazda Jenab, Catherine Méplan, Jeb Jones, Wanzhe Zhu, et al.. Association of Selenoprotein and Selenium Pathway Genotypes with Risk of Colorectal Cancer and Interaction with Selenium Status. Nutrients, 2019, 11 (4), pp.935. ⟨10.3390/nu11040935⟩. ⟨hal-02153500⟩