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Protein expressions and genetic variations of SLC5A8 in prostate cancer risk and aggressiveness.

ABSTRACT: To understand the role in prostate cancer risk and aggressiveness, we investigated the expression in prostate tumor and single nucleotide polymorphisms of SLC5A8. Previous studies have suggested that SLC5A8 might function as a tumor suppressor gene, whose silencing by epigenetic changes might contribute to carcinogenesis.We constructed tissue microarrays from 183 prostate tumor tissues, 43 adjacent non-neoplastic tissues from the same patients, and 13 tissue samples from patients with benign prostatic hyperplasia or prostatic intraepithelial neoplasia. A semiquantitative assessment of SLC5A8 protein expression was determined as the product of immunostaining intensity and the percentage of cells stained. In addition, we compared the frequencies of 4 single nucleotide polymorphisms (rs164365, rs1709189, rs1399236, and rs1681096) in SLC5A8 between 668 prostate cancer cases and 385 controls.SLC5A8 expression was significantly greater in the tumor tissues than in the paired non-neoplastic tissues (P < .0001). In the Moffitt samples, we observed a borderline moderate risk increase in patients with a genotype containing ?1 "A" allele of rs164365 (odds ratio 1.35, 95% confidence interval 1.00-1.80), especially among tall men (?70 in.; odds ratio 1.80, 95% confidence interval 1.20-2.68). However, these results were not confirmed in the Cancer Genetic Markers of Susceptibility population.These data suggest that the expression pattern of SLC5A8 might be used as a diagnostic biomarker, and a larger study is required to assess the importance of SLC5A8 single nucleotide polymorphisms in prostate cancer.

SUBMITTER: Lin HY

PROVIDER: S-EPMC3190039 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Protein expressions and genetic variations of SLC5A8 in prostate cancer risk and aggressiveness.

Lin Hui-Yi HY Park Hyun Y HY Radlein Selina S Mahajan Nupam P NP Sellers Thomas A TA Zachariah Babu B Pow-Sang Julio J Coppola Domenico D Ganapathy Vadivel V Park Jong Y JY

Urology 20110729 4

<h4>Objective</h4>To understand the role in prostate cancer risk and aggressiveness, we investigated the expression in prostate tumor and single nucleotide polymorphisms of SLC5A8. Previous studies have suggested that SLC5A8 might function as a tumor suppressor gene, whose silencing by epigenetic changes might contribute to carcinogenesis.<h4>Methods</h4>We constructed tissue microarrays from 183 prostate tumor tissues, 43 adjacent non-neoplastic tissues from the same patients, and 13 tissue sam ...[more]

PMID: 21802122

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Project description:BACKGROUND:Genetic variations in some of the selenoprotein genes, alone or together with an individual's selenium status, may influence risk or progression of prostate cancer. We investigated the impact of genetic variants of selenoproteins on plasma selenium levels and cancer aggressiveness at diagnosis in men with localized prostate cancer (PCa). METHODS:The study cohort comprised 722 patients seen at Dana-Farber Cancer Institute who had localized/locally advanced PCa (i.e., stage T3 or less, N0, and M0) from 1994 to 2001. Fifty-five tagging single nucleotide polymorphisms (SNPs) from six selenoprotein genes (TXNRD1, TXNRD2, SEP15, GPX3, SELENBP1, and SEPP1) were analyzed. Logistic regression is used to examine associations of genotypes and plasma selenium levels with risk of aggressive disease, defined as D'Amico intermediate/high risk categories. Step down permutation was applied to adjust for multiple comparisons. RESULTS:Three hundred and forty-eight patients (48%) had aggressive disease at diagnosis. Two SNPs were associated with cancer aggressiveness at diagnosis (unadjusted P?=?0.017 and 0.018, respectively). The odds ratio for aggressive disease in patients carrying TXNRD2 rs1005873-AG/GG genotypes or SELENBP1 rs10788804-AG/AA genotypes was 1.54 (95% CI?=?1.08, 2.20) and 1.45 (95% CI?=?1.07, 1.98), respectively, compared to TXNRD2 rs1005873-AA or SELENBP1 rs10788804-GG carriers. Four SNPs in TXNRD2 (rs1005873, rs13054371, rs3788310, and rs9606174) and the rs230820 in SEPP1 were associated with plasma selenium levels (unadjusted P?<?0.05). Permutation adjusted P-values were not statistically significant for all these comparisons at the cut-off point of 0.05. CONCLUSION:We identified polymorphisms in selenoproteins that may influence the plasma selenium levels and may be associated with the risk of presenting with aggressive PCa in men with localized or locally advanced PCa. These results should be validated in other independent datasets.

Dataset Information

Protein expressions and genetic variations of SLC5A8 in prostate cancer risk and aggressiveness.

Publications

Protein expressions and genetic variations of SLC5A8 in prostate cancer risk and aggressiveness.

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