Association of Selenoprotein and Selenium Pathway Genotypes with Risk of Colorectal Cancer and Interaction with Selenium Status
| Autor: | Fedirko, Veronika, Jenab, Mazda, Méplan, Catherine, Jones, Jeb S, Zhu, Wanzhe, Schomburg, Lutz, Siddiq, Afshan, Hybsier, Sandra, Overvad, Kim, Tjønneland, Anne, Omichessan, Hanane, Perduca, Vittorio, Boutron-Ruault, Marie-Christine, Kühn, 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 CH, Weiderpass, Elisabete, Skeie, Guri, Nøst, Therese Haugdahl, Lujan-Barroso, Leila, Quirós, J Ramón, Huerta, José María, Rodríguez-Barranco, Miguel, Barricarte, Aurelio, Gylling, Björn, 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 |
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| Předmět: |
Adult
Male genetic epidemiology Genotype selenoprotein P prospective cohort Nutritional Status selenoprotein gene variation Polymorphism Single Nucleotide Cohort Studies Selenium Humans Genetic Predisposition to Disease Prospective Studies Selenoproteins Aged integumentary system colorectal cancer risk biomarkers colorectal neoplasms Middle Aged 3. Good health selenium pathway Gene Expression Regulation selenium status Female |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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