Polymorphisms in thioredoxin reductase and selenoprotein k genes and selenium status modulate risk of prostate cancer
Autor: | Lutz Schomburg, Catherine Méplan, John E. Hesketh, Astrid Steinbrecher, Jakob Linseisen, Eugène H.J.M. Jansen, Sabine Rohrmann |
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Jazyk: | angličtina |
Rok vydání: | 2012 |
Předmět: |
Male
Oncology Heredity Non-Clinical Medicine Epidemiology Gene Expression Genome-wide association study Bioinformatics Biochemistry Prostate cancer Cancer screening Genotype Selenoproteins chemistry.chemical_classification Molecular Epidemiology Multidisciplinary Prostate Cancer Selenoprotein P Genetic Epidemiology Micronutrient Deficiencies Disease Progression Medicine Cancer Epidemiology Research Article Nutrient and Storage Proteins medicine.medical_specialty Thioredoxin-Disulfide Reductase Science Genotypes Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide Selenium Genetic Mutation Internal medicine Genetics Cancer Genetics medicine Humans ddc:610 Genotyping Nutrition Glutathione Peroxidase Models Statistical Polymorphism Genetic Health Care Policy Models Genetic Prostatic Neoplasms Proteins Health Risk Analysis Cancers and Neoplasms medicine.disease Genitourinary Tract Tumors Metabolism chemistry Case-Control Studies Genetics of Disease Selenoprotein |
Zdroj: | PLoS ONE 7:e48709 (2012) PLoS ONE, Vol 7, Iss 11, p e48709 (2012) PLoS ONE |
Popis: | Increased dietary intake of Selenium (Se) has been suggested to lower prostate cancer mortality, but supplementation trials have produced conflicting results. Se is incorporated into 25 selenoproteins. The aim of this work was to assess whether risk of prostate cancer is affected by genetic variants in genes coding for selenoproteins, either alone or in combination with Se status. 248 cases and 492 controls from an EPIC-Heidelberg nested case-control study were subjected to two-stage genotyping with an initial screening phase in which 384 tagging-SNPs covering 72 Se-related genes were determined in 94 cases and 94 controls using the Illumina Goldengate methodology. This analysis was followed by a second phase in which genotyping for candidate SNPs identified in the first phase was carried out in the full study using Sequenom. Risk of high-grade or advanced stage prostate cancer was modified by interactions between serum markers of Se status and genotypes for rs9880056 in SELK, rs9605030 and rs9605031 in TXNRD2, and rs7310505 in TXNRD1. No significant effects of SNPs on prostate cancer risk were observed when grade or Se status was not taken into account. In conclusion, the risk of high-grade or advanced-stage prostate cancer is significantly altered by a combination of genotype for SNPs in selenoprotein genes and Se status. The findings contribute to explaining the biological effects of selenium intake and genetic factors in prostate cancer development and highlight potential roles of thioredoxin reductases and selenoprotein K in tumour progression. |
Databáze: | OpenAIRE |
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