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Selenoprotein P genetic variants and mrna expression, circulating selenium, and prostate cancer risk and survival.
Prostate 2013; 73(7):700-5P

Abstract

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.

Authors+Show Affiliations

Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. kpenney@hsph.harvard.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

23129481

Citation

Penney, Kathryn L., et al. "Selenoprotein P Genetic Variants and Mrna Expression, Circulating Selenium, and Prostate Cancer Risk and Survival." The Prostate, vol. 73, no. 7, 2013, pp. 700-5.
Penney KL, Li H, Mucci LA, et al. Selenoprotein P genetic variants and mrna expression, circulating selenium, and prostate cancer risk and survival. Prostate. 2013;73(7):700-5.
Penney, K. L., Li, H., Mucci, L. A., Loda, M., Sesso, H. D., Stampfer, M. J., & Ma, J. (2013). Selenoprotein P genetic variants and mrna expression, circulating selenium, and prostate cancer risk and survival. The Prostate, 73(7), pp. 700-5. doi:10.1002/pros.22611.
Penney KL, et al. Selenoprotein P Genetic Variants and Mrna Expression, Circulating Selenium, and Prostate Cancer Risk and Survival. Prostate. 2013;73(7):700-5. PubMed PMID: 23129481.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Selenoprotein P genetic variants and mrna expression, circulating selenium, and prostate cancer risk and survival. AU - Penney,Kathryn L, AU - Li,Haojie, AU - Mucci,Lorelei A, AU - Loda,Massimo, AU - Sesso,Howard D, AU - Stampfer,Meir J, AU - Ma,Jing, Y1 - 2012/11/05/ PY - 2012/08/08/received PY - 2012/10/05/accepted PY - 2012/11/7/entrez PY - 2012/11/7/pubmed PY - 2013/6/29/medline SP - 700 EP - 5 JF - The Prostate JO - Prostate VL - 73 IS - 7 N2 - 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. SN - 1097-0045 UR - https://www.unboundmedicine.com/medline/citation/23129481/Selenoprotein_P_genetic_variants_and_mrna_expression_circulating_selenium_and_prostate_cancer_risk_and_survival_ L2 - https://doi.org/10.1002/pros.22611 DB - PRIME DP - Unbound Medicine ER -