Journal
NUTRIENTS
Volume 11, Issue 4, Pages -Publisher
MDPI
DOI: 10.3390/nu11040935
Keywords
selenium; selenium status; selenoprotein gene variation; selenium pathway; colorectal neoplasms; selenoprotein P; prospective cohort; colorectal cancer risk; genetic epidemiology; biomarkers
Categories
Funding
- Health Research Board of Ireland health research [HRA_PHS/2013/397, HRA_PHS/2015/1142]
- Europe Against Cancer Programme of the European Commission (SANCO)
- Ligue contre le Cancer
- Institut Gustave Roussy
- Mutuelle Generale de l'Education Nationale
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- German Cancer Aid
- German Cancer Research Center
- German Federal Ministry of Education and Research
- Danish Cancer Society
- Health Research Fund (FIS) of the Spanish Ministry of Health
- CIBER en Epidemiologia y Salud Publica (CIBERESP), Spain
- ISCIII RETIC [RD06/0020]
- Catalan Institute of Oncology
- Cancer Research UK
- Medical Research Council, UK
- Hellenic Health Foundation
- Italian Association for Research on Cancer
- Italian National Research Council
- Compagnia di San Paolo
- Dutch Prevention Funds (The Netherlands)
- Dutch ZON (ZorgOnderzoek Nederland) (The Netherlands)
- World Cancer Research Fund (WCRF) (The Netherlands)
- Statistics Netherlands (The Netherlands)
- Swedish Cancer Society
- Swedish Scientific Council
- Regional Government of Skane, Sweden
- Regional Government of Vasterbotten, Sweden
- Nordforsk center of excellence programme HELGA
- Deutsche Forschungsgemeinschaft (DFG Research Unit 2558 TraceAge) [Scho 849/6-1]
- Associazione Italiana per la Ricercasul Cancro-AIRC-Italy
- Spanish Regional Government of Andalusia
- Spanish Regional Government of Asturias
- Spanish Regional Government of Basque Country
- Spanish Regional Government of Murcia [6236]
- Spanish Regional Government of Navarra
- Dutch Ministry of Public Health, Welfare and Sports (VWS) (The Netherlands)
- Netherlands Cancer Registry (NKR) (The Netherlands)
- LK Research Funds (The Netherlands)
- MRC [MC_UU_12015/1, MR/N003284/1] Funding Source: UKRI
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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 (P-ACT = 0.10; P-ACT 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.
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