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Article details
Title
Interaction between Single Nucleotide Polymorphisms in Selenoprotein P and Mitochondrial Superoxide Dismutase Determines Prostate Cancer Risk
Published in
Cancer Research, December 2008
DOI 10.1158/0008-5472.can-08-1827
Pubmed ID
Authors
Abstract

Selenium may affect prostate cancer risk via its plasma carrier selenoprotein P which shows dramatically reduced expression in prostate cancer tumors and cell lines. The selenoprotein P (SEPP1) Ala234 single nucleotide polymorphism (SNP) allele is associated with lower plasma selenoprotein P in men, reducing the concentration/activity of other antioxidant selenoproteins. Selenium status also modifies the effect of the mitochondrial superoxide dismutase (SOD2) SNP Ala16Val on prostate cancer risk. We investigated the relationship of these SNPs with prostate cancer risk. DNA from 2,975 cases and 1,896 age-matched controls from the population-based Prostate Cancer in Sweden study were genotyped using TaqMan assays. Cases were designated aggressive or nonaggressive prostate cancers at diagnosis by clinical criteria. Association with prostate cancer was investigated by logistic regression; gene-gene interaction using a general linear model. The mean plasma selenium concentration measured in 169 controls was relatively low (76.0 +/- 17.2 microg/L). SNP genotype distributions were in Hardy-Weinberg equilibrium. SOD2-Ala16+ men were at a greater risk of prostate cancer [odds ratios (OR), 1.19; 95% confidence intervals (CI), 1.03-1.37] compared with SOD2-Val16 homozygotes. Men homozygous for SEPP1-Ala234 who were also SOD2-Ala16+ had a higher risk of prostate cancer (OR, 1.43; 95% CI, 1.17-1.76) and aggressive prostate cancer (OR, 1.60; 95% CI, 1.22-2.09) than those who were SOD2-Val16 homozygotes (interaction, prostate cancer P = 0.05; aggressive prostate cancer P = 0.01). This interaction was stronger in ever-smokers: SOD2-Ala16+ men homozygous for SEPP1-Ala234 had an almost doubled risk of prostate cancer (OR, 1.97; 95% CI, 1.33-2.91; interaction P = 0.001). In a low-selenium population, SOD2-Ala16+ men homozygous for SEPP1-Ala234 are at an increased risk of prostate cancer/aggressive prostate cancer especially if ever-smokers, because they are likely to produce more mitochondrial H(2)O(2) that they cannot remove, thereby promoting prostate tumor cell proliferation and migration.

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X Demographics

X Demographics

The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Mendeley demographics

Mendeley demographics

The data shown below were compiled from readership statistics for 57 Mendeley readers of this research output. Click here to see the associated Mendeley record.
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Geographical breakdown

Geographical breakdown
Country Count As %
United States 2 4%
Spain 1 2%
Unknown 54 95%

Demographic breakdown

Readers by professional status
Readers by professional status Count As %
Student > Ph. D. Student 14 25%
Student > Bachelor 7 12%
Researcher 7 12%
Student > Master 5 9%
Student > Doctoral Student 4 7%
Other 14 25%
Unknown 6 11%
Readers by discipline
Readers by discipline Count As %
Agricultural and Biological Sciences 18 32%
Biochemistry, Genetics and Molecular Biology 9 16%
Medicine and Dentistry 9 16%
Pharmacology, Toxicology and Pharmaceutical Science 2 4%
Chemistry 2 4%
Other 6 11%
Unknown 11 19%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 27 January 2013.
All research outputs
#15,262,171
of 22,694,633 outputs
Outputs from Cancer Research
#14,381
of 17,840 outputs
Outputs of similar age
#139,750
of 166,867 outputs
Outputs of similar age from Cancer Research
#176
of 187 outputs
Altmetric has tracked 22,694,633 research outputs across all sources so far. This one is in the 22nd percentile – i.e., 22% of other outputs scored the same or lower than it.
So far Altmetric has tracked 17,840 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.7. This one is in the 13th percentile – i.e., 13% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 166,867 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 7th percentile – i.e., 7% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 187 others from the same source and published within six weeks on either side of this one. This one is in the 2nd percentile – i.e., 2% of its contemporaries scored the same or lower than it.