title: Selenoprotein gene variants, toenail selenium levels, and risk for advanced prostate cancer.
abstract: Lower selenium levels have been associated with increased risk of prostate cancer (PCa), and genetic variation in the selenoprotein genes selenoprotein P (SEPP1) and glutathione peroxidase 1 (GPX1) is thought to modify this relationship. We investigated whether the association between toenail selenium levels and advanced PCa risk in the prospective Netherlands Cohort Study is modified by common genetic variation in SEPP1 and GPX1. Toenail clippings were used to determine selenium levels and to isolate DNA for genotyping. This case-cohort study, which included 817 case subjects with advanced PCa and 1048 subcohort members, was analyzed with Cox regression models. All statistical tests were two-sided. Three genetic variants were associated with advanced (stage III/IV or IV) PCa risk: SEPP1 rs7579 (lower risk; P trend = .01), GPX1 rs17650792 (higher risk; P trend = .03), and GPX1 rs1800668 (lower risk; P trend = .005). Toenail selenium levels were inversely associated with advanced PCa risk, independently of common genetic variation in SEPP1 and GPX1.
authors.affiliation: Affiliations of authors: Department of Epidemiology (MSG, PvdB, LS, BV) and Department of Toxicogenomics (SvB), GROW School for Oncology and Developmental Biology, and Department of Toxicology (FvS), NUTRIM School for Nutrition, Toxicology, and Metabolism, Maastricht University, Maastricht, the Netherlands; Department of Nutritional Sciences (MR) and Department of Biochemistry and Physiology (FG), Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK.
authors.forename: Milan S
authors.initials: MS
authors.lastname: Geybels
authors.forename: Piet A
authors.initials: PA
authors.lastname: van den Brandt
authors.forename: Leo J
authors.initials: LJ
authors.lastname: Schouten
authors.forename: Frederik J
authors.initials: FJ
authors.lastname: van Schooten
authors.forename: Simone G
authors.initials: SG
authors.lastname: van Breda
authors.forename: Margaret P
authors.initials: MP
authors.lastname: Rayman
authors.forename: Fiona R
authors.initials: FR
authors.lastname: Green
authors.forename: Bas A J
authors.initials: BA
authors.lastname: Verhage
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D005979:Glutathione Peroxidase / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009262:Nails / Q000378:metabolism*; D009367:Neoplasm Staging; D009426:Netherlands / Q000453:epidemiology; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D018570:Risk Assessment; D012307:Risk Factors; D012643:Selenium / Q000378:metabolism*; D051140:Selenoproteins / Q000235:genetics* / Q000378:metabolism; D000094765:Glutathione Peroxidase GPX1
chemical_list: D051140:Selenoproteins; D005979:Glutathione Peroxidase; D012643:Selenium; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human