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Association of Selenoprotein and Selenium Pathway Genotypes with Risk of Colorectal Cancer and Interaction with Selenium Status
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2019 (English)In: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 11, no 4, article id 935Article in journal (Refereed) Published
Abstract [en]

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 Goldengateassays 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.

Place, publisher, year, edition, pages
MDPI, 2019. Vol. 11, no 4, article id 935
Keywords [en]
selenium, selenium status, selenoprotein gene variation, selenium pathway, colorectal neoplasms, selenoprotein P, prospective cohort, colorectal cancer risk, genetic epidemiology, biomarkers
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Nutrition and Dietetics
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URN: urn:nbn:se:umu:diva-159879DOI: 10.3390/nu11040935ISI: 000467749800228PubMedID: 31027226OAI: oai:DiVA.org:umu-159879DiVA, id: diva2:1321963
Funder
Swedish Cancer SocietySwedish Research CouncilRegion SkåneVästerbotten County CouncilAvailable from: 2019-06-10 Created: 2019-06-10 Last updated: 2019-06-10Bibliographically approved

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Gylling, BjörnHarlid, Sophia

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