OA Epidemiology

Selenoprotein P and glutathione peroxidase 1 genetic variants, toenail selenium status, and risk of advanced prostate cancer

Proceedings of the 2013 annual meeting of the Netherlands Epidemiology Society

Volume 1 Issue S1 Abstract 59

 

M.S. Geybels, GROW, Maastricht University, Maastricht, the Netherlands
P.A. van den Brandt, GROW, Maastricht University, Maastricht, the Netherlands
L.J. Schouten, GROW, Maastricht University, Maastricht, the Netherlands
F.J. van Schooten, NUTRIM, Maastricht University, Maastricht, the Netherlands
B.A.J. Verhage, GROW, Maastricht University, Maastricht, the Netherlands

Background
The major selenoproteins, selenoprotein P (SEPP1) and glutathione peroxidase 1 (GPX1) may play a role in prostate cancer (PCa) either independently or by modifying the effects of selenium. We investigated common genetic variation in SEPP1 and  GPX1 in relation to advanced PCa risk and examined the interaction with toenail selenium status.

Methods
We conducted a case-cohort analysis among 58,279 men (aged 55-69 years) in the Netherlands Cohort study. Toenail samples were used as a source of DNA for genotyping and to determine selenium levels. We evaluated eight tagging single nucleotide polymorphisms (SNPs) in SEPP1 (n=5)  and  GPX1 (n=3).  Incident advanced (stage III/IV) PCa cases were identified during 17.3 years of follow-up. Cox proportional hazards regression models were used.

Results
The analysis included 952 advanced PCa cases and 1,757  subcohort members with genotyping data. SEPP1 rs7579 was associated with stage IV PCa risk (HRGG = 1.00 (reference), HRAG = 0.81 (95% CI: 0.66-0.99),  HRAA = 0.71 (95% CI: 0.51-1.00)). Two GPX1 SNPs were associated with advanced (stage III/IV) PCa risk; GPX1 rs17650792  (HRAA = 1.00 (reference), HRAG = 1.14 (95% CI: 0.95-1.37),  HRGG = 1.29 (95% CI: 1.01-1.63)) and GPX1 rs1800668 (HRCC = 1.00 (reference), HRCT = 0.81 (95% CI: 0.68-0.96), HRTT = 0.73 (95% CI: 0.54-0.97)). The HRs were not different for stage IV PCa. There were  no statistically significant interactions for genotype and toenail selenium status.

Conclusions
Genetic variants in SEPP1 and  GPX1 were associated with advanced PCa risk; there were no interactions with toenail selenium status.

Published: 06 Jun, 2013

 
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