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Selenoprotein P genetic variants and mrna expression, circulating selenium, and prostate cancer risk and survival
Author(s) -
Penney Kathryn L.,
Li Haojie,
Mucci Lorelei A.,
Loda Massimo,
Sesso Howard D.,
Stampfer Meir J.,
Ma Jing
Publication year - 2013
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.22611
Subject(s) - selenoprotein p , selenoprotein , single nucleotide polymorphism , prostate cancer , hazard ratio , medicine , minor allele frequency , selenium , oncology , odds ratio , genotype , allele , endocrinology , cancer , biology , genetics , confidence interval , gene , glutathione peroxidase , oxidative stress , chemistry , catalase , organic chemistry
BACKGROUND Low levels of selenium have been associated with increased risk of prostate cancer (PCa). Selenoprotein P is the most abundant selenoprotein in serum and delivers ten selenocysteine residues to tissues. Variation in the selenoprotein P gene ( SEPP1 ) may influence PCa development or modify the effects of selenium. We examined the association of SEPP1 single nucleotide polymorphisms (SNPs) with PCa risk and survival, and tested for interactions. METHODS The Physicians' Health Study (PHS) is a prospective cohort of 22,071 US physicians; we utilized a nested case–control study of 1,352 PCa cases and 1,382 controls. We assessed four SNPs capturing common variation within the SEPP1 locus. In a subset of men (n = 80), we evaluated SEPP1 mRNA expression in tumors. RESULTS Two SNPs were significantly associated with PCa risk. For rs11959466, each T allele increased risk (odds ratio (OR) = 1.31; 95% confidence interval (CI): 1.02,1.69; P trend = 0.03). For rs13168440, the rare homozygote genotype decreased risk compared to the common homozygote (OR = 0.56, 95% CI: 0.33, 0.96). Moreover, there was a significant interaction of rs13168440 with plasma selenium; increasing selenium levels were associated with decreased PCa risk only among men with the minor allele ( P interaction = 0.01). SEPP1 expression was significantly lower in men with lethal PCa than long‐term survivors. CONCLUSIONS SEPP1 genetic variation was associated with PCa incidence; replication of these results in an independent dataset is necessary. These findings further support a causal link between selenium and PCa, and suggest that the effect of selenium may differ by genetics. Prostate 73: 700–705, 2013. © 2012 Wiley Periodicals, Inc.