@article { , title = {Association of selenoprotein and selenium pathway genotypes with risk of colorectal cancer and interaction with selenium status.}, 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.}, doi = {10.3390/nu11040935}, eissn = {2072-6643}, issue = {4}, journal = {Nutrients}, note = {INFO COMPLETE (checked 3/5/2019 LM -- Info via Jisc Pub 30/4/2019) PERMISSION GRANTED (version = VoR; embargo = none; licence = BY) DOCUMENT RECEIVED (VoR downloaded 3/5/2019 LM) ADDITIONAL INFORMATION: On Alma as visiting professor. Outlook contact info suggests VPR org unit.}, publicationstatus = {Published}, publisher = {MDPI}, url = {https://rgu-repository.worktribe.com/output/240451}, volume = {11}, keyword = {Health & Wellbeing, Selenium, Selenium status, Selenoprotein gene variation, Selenium pathway, Colorectal neoplasms, Selenoprotein P, Prospective cohort, Colorectal cancer risk, Genetic epidemiology, Biomarkers}, year = {2019}, author = {Fedirko, Veronika and Jenab, Mazda and Méplan, Catherine and Jones, Jeb S. and Zhu, Wanzhe and Schomburg, Lutz and Siddiq, Afshan and Hybsier, Sandra and Overvad, Kim and Tjønneland, Anne and Omichessan, Hanane and Perduca, Vittorio and Boutron-Ruault, Marie-Christine and Kühn, Tilman and Katzke, Verena and Aleksandrova, Krasimira and Trichopoulou, Antonia and Karakatsani, Anna and Kotanidou, Anastasia and Tumino, Rosario and Panico, Salvatore and Masala, Giovanna and Agnoli, Claudia and Naccarati, Alessio and Bueno-de-Mesquita, Bas and Vermeulen, Roel C.H. and Weiderpass, Elisabete and Skeie, Guri and Nøst, Therese Haugdahl and Lujan-Barroso, Leila and Quirós, J. Ramón and Huerta, José María and Rodríguez-Barranco, Miguel and Barricarte, Aurelio and Gylling, Björn and Harlid, Sophia and Bradbury, Kathryn E. and Wareham, Nick and Khaw, Kay-Tee and Gunter, Marc and Murphy, Neil and Freisling, Heinz and Tsilidis, Kostas and Aune, Dagfinn and Riboli, Elio and Hesketh, John E. and Hughes, David J.} }