Level of selenoprotein transcripts in peripheral leukocytes of patients with bladder cancer and healthy individuals

Abstract

Background: Low concentrations of selenium (Se) in humans have been associated with risk of cancer. Selenoprotein mRNAs can potentially be regulated by Se status. Methods: Se status, GPx1 Pro198Leu and Sep15 1125G/A genetic polymorphism and human (h)GPx1, hGPx3, hSep15 and hSeP1 transcript levels in peripheral leukocytes of 33 males with bladder cancer and 47 healthy male controls were analysed. Results: All the subjects expressed detectable selenoprotein mRNA concentrations in leukocytes. Significantly lower expression of hGPx1, hGPx3, hSep15 and hSeP1 in leukocytes of bladder cancer patients compared to controls was observed. hGPx1, hGPx3 and hSep15 expression was significantly lower in non-smokers in the control group compared with smokers in the control group. A positive relationship between expression of all studied genes was also observed in non-smoking controls. Expression of hGPx3 and hSep15 gradually increased with tumour grade in patients with cancer. We did not find any association between selenoprotein mRNA levels, Se status and selenoprotein genetic polymorphism. Conclusions: This study showed significant downregulation of hGPx1, hGPx3, hSep15 and hSeP1 mRNA levels in leukocytes of patients with bladder cancer compared to controls. Selenoprotein transcript levels in circulating leukocytes of patients with bladder cancer and controls revealed no potential impact of Se status on selenoprotein expression.

The 811 C/T polymorphism in the 3′ untranslated region of the selenoprotein 15-kDa (Sep15) gene and breast cancer in Caucasian women

“…Of note, the T allele, associated with an increased risk of breast cancer in African women [16], colorectal cancer in Asian men [23], and lung cancer in Caucasians with low Se levels [11], occurs generally more often in African-Americans (31 vs. 7 %) [16]. Therefore, similar to other studies [30,40,41], our results can be impacted by the overall lower presence of the T allele in Caucasians (2-2.4 % TT homozygotes in our data sets).…”

“…In animal models, changes in the Sep15 structure promoted the experimental carcinogenesis in the mammary gland in mice [21,22]. However, as shown in Table 3, the described link between Sep15 Hu [16] Breast 60 African-American (USA) Increased cancer risk in CG/CG homozygotes Hu [16] Head and neck 33 African-American (USA) Decreased risk in CG/TA heterozygotes Hu [16] Head and neck 94 Caucasian (USA) No association Hu [16] Chronic myelogenous leukemia No association for SEP15 alone; two-loci interaction between SEPP1 and SEP15 3′-UTR polymorphisms and cancer susceptibility is not obvious [11,16,[23][24][25][26][30][31][32][33].…”

“…Data regarding the relationship between Se, Sep15 expression, and Sep15 gene polymorphisms are conflicting. It has been proposed that the expression of Sep15 could be regulated in response to dietary Se intake [12,14], but recently, the expression of Sep15 has been shown not to depend on serum Se concentration in Caucasian males with bladder cancer [30] or healthy volunteers [42]. Serum Se concentration may modify the effect of Sep15 gene polymorphisms on lung cancer development.…”

GPx-1 polymorphism (rs1050450) contributes to tumor susceptibility: evidence from meta-analysis

“…Thereafter, emerging studies have been done to evaluate the association between GPx-1 Pro198Leu polymorphism and risks for diVerent types of tumor in diverse populations, such as breast cancer (Ravn-Haren et al 2006;Cox et al 2004;Ahn et al 2005;Hu and Diamond 2003;Knight et al 2004;Cebrian et al 2006), lung cancer (Rosenberger et al 2008;Yang et al 2004;Ratnasinghe et al 2000;RaaschouNielsen et al 2007;Skuladottir et al 2005;Lee et al 2006), bladder cancer (Ichimura et al 2004;Paz-y-Mino et al 2010;Reszka et al 2009;Goerlitz et al 2011), prostate cancer (Choi et al 2007;Arsova-SaraWnovska et al 2009;Steinbrecher et al 2010), colorectal cancer Hansen et al 2005Hansen et al , 2009 and other cancers (Rajaraman et al 2008;Bhatti et al 2009;Wang et al 2008;Hu et al 2004;Ezzikouri et al 2010;Lightfoot et al 2006;Wu et al 2010;Tang et al 2010;Vogel et al 2004;He et al 2011). However, the results from those studies remain debatable rather than conclusive.…”

Selenium and cancer

“…On the other hand, a number of studies failed to find such relationships, or only found it in specific subgroups, such as smokers [11][12][13][14][15] .…”