BackgroundSince targeting oxidative stress markers has been recently recognized as a novel therapeutic target in cancer, it is interesting to investigate whether genetic susceptibility may modify oxidative stress response in cancer. The aim of this study was to elucidate whether genetic polymorphism in the antioxidant enzymes is associated with lipid peroxidation in breast cancer.MethodsWe conducted a study among Polish women, including 136 breast cancer cases and 183 healthy controls. The analysis included genetic polymorphisms in five redox related genes: GPX1 (rs1050450), GPX4 (rs713041), SOD2 (rs4880), SEPP1 (rs3877899) and SEP15 (rs5859), lipid peroxidation, the activities of antioxidant enzymes determined in blood compartments as well as plasma concentration of selenium – an antioxidant trace element involved in cancer. Genotyping was performed using the Real Time PCR. Lipid peroxidation was expressed as plasma concentration of thiobarbituric acid reactive substances (TBARS) and measured with the spectrofluorometric method. Glutathione peroxidase activity was spectrophotometrically determined in erythrocytes (GPx1) and plasma (GPx3) by the use of Paglia and Valentine method. Spectrophotometric methods were employed to measure activity of cytosolic superoxide dismutase (SOD1) in erythrocytes (Beauchamp and Fridovich method) and ceruloplasmin (Cp) in plasma (Sunderman and Nomoto method). Plasma selenium concentration was determined using graphite furnace atomic absorption spectrophotometry.ResultsBreast cancer risk was significantly associated with GPX1 rs1050450 (Pro198Leu) polymorphism, showing a protective effect of variant (Leu) allele. As compared to the control subjects, lipid peroxidation and GPx1 activity were significantly higher in the breast cancer cases, whereas ceruloplasmin activity was decreased. After genotype stratification, both GPx1 activity and TBARS concentration were the highest in GPX1 Pro/Pro homozygotes affected by breast cancer. At the same time, there was a significant correlation between the level of lipid peroxidation and GPx1 activity among the cancer subjects possessing GPX1 Pro/Pro genotype (r = 0.3043; p = 0.0089), whereas such a correlation was completely absent in the cases carrying at least one GPX1 Leu allele as well as in the controls (regardless of GPX1 genotype).ConclusionsGPX1 polymorphism may be an important factor modifying oxidative stress response in breast cancer subjects. Further studies are needed to elucidate its potential clinical significance.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1680-4) contains supplementary material, which is available to authorized users.

Objectives• To elucidate genetic polymorphisms of the matrix metalloproteinases (MMPs) MMP1 (rs1799750), MMP2 (rs243865), MMP9 (rs3918242), MMP12 (rs2276109) and tissue inhibitors of MMPs (TIMPs) TIMP1 (rs2070584) and TIMP3 (rs9619311) genes that may be involved in susceptibility to bladder cancer (BC). Patients and Methods• We enrolled 241 patients with BC and 199 controls.• Genomic DNA samples were extracted from peripheral blood and polymorphisms were analysed by high-resolution melting analysis and by real-time polymerase chain reaction using TaqMan fluorescent probes. T with MMP9 -1562C/T (rs3918242) allele T was found to increase BC risk (OR 2.00, 95% CI 1.10-3.62; P = 0.022). Results • Of the six evaluated polymorphisms of Conclusions• Our results suggest that genetic variations in five polymorphisms of MMPs and TIMPs are not associated with a high risk of BC.• Only MMP1 polymorphism may be related to the risk of BC, notably in 'ever smokers' . • Our study suggests that the effects of polymorphisms of MMPs and TIMPs on BC risk deserve further investigation.

PurposeNRF2 transcription factor is involved in modulation of various antioxidant and metabolic genes and, therefore, may modulate anti-carcinogenic potential. Association between polymorphisms of NRF2 and five NRF2-regulated genes and urinary bladder cancer (BC) risk was analyzed.MethodsThe study group included 244 BC patients, while the control group comprised 365 individuals with no evidence of malignancy. Genotyping of GSTM1 (deletion), GSTT1 (deletion), GSTA1 −69C/T (rs3957357), GSTP1 Ile105Val (rs1695), SOD2 Ala16Val (rs4880) and NRF2 −617C/A (rs6721961) in blood genomic DNA was performed by means of real-time PCR assays. The associations between gene polymorphism and BC risk were computed by logistic regression.ResultsThe frequency of GSTA1, GSTP1, SOD2 and NRF2 genotypes did not differ in both groups. A significantly higher BC risk was associated with GSTM1 null genotype after adjusting to age, sex and smoking habit (OR 1.85, 95 % CI 1.30–2.62; P = 0.001). GSTT1 null (OR 0.50, 95 % CI 0.31–0.81; P = 0.005) and GSTP1 Val105Val (OR 0.52, 95 % CI 0.27–0.98; P = 0.04) genotypes were associated with reduced BC risk separately or in combination (OR 0.24, 95 % CI 0.11–0.51; P < 0.0001) (P heterogeneity = 0.01). Combined GSTT1 null and SOD2 with at least one 16Val allele among never smokers encompass reduced BC risk (OR 0.14, 95 % CI 0.03–0.63; P = 0.01) (P heterogeneity = 0.04).ConclusionsThis study supports hypothesis that GSTM1 null genotype may be a moderate BC risk factor. The gene–gene and gene–environment interactions associated with combined GSTP1/GSTT1 and combined GSTT1/SOD2 genetic polymorphisms along with cigarette smoking habit may play a significant role in BC risk modulation.

The aim of the study was to evaluate the effect of selenium supplementation on the expression of genes associated with glucose metabolism in humans, in order to explain the unclear relationship between selenium and the risk of diabetes. For gene expression analysis we used archival samples of cDNA from 76 non-diabetic subjects supplemented with selenium in the previous study. The supplementation period was six weeks and the daily dose of selenium was 200 µg (as selenium yeast). Blood for mRNA isolation was collected at four time points: before supplementation, after two and four weeks of supplementation, and after four weeks of washout. The analysis included 15 genes encoding selected proteins involved in insulin signaling and glucose metabolism. In addition, HbA1c and fasting plasma glucose were measured at three and four time points, respectively. Selenium supplementation was associated with a significantly decreased level of HbA1c but not fasting plasma glucose (FPG) and significant down-regulation of seven genes: INSR, ADIPOR1, LDHA, PDHA, PDHB, MYC, and HIF1AN. These results suggest that selenium may affect glycemic control at different levels of regulation, linked to insulin signaling, glycolysis, and pyruvate metabolism. Further research is needed to investigate mechanisms of such transcriptional regulation and its potential implication in direct metabolic effects.

PurposeSelenium, both essential and toxic element, is considered to protect against cancer, though human supplementation trials have generated many inconsistent data. Genetic background may partially explain a great variability of the studies related to selenium and human health. The aim of this study was to assess whether functional polymorphisms within two selenoprotein-encoding genes modify the response to selenium at the level of oxidative stress, DNA damage, and mRNA expression, especially in the individuals with a relatively low selenium status.MethodsThe trial involved 95 non-smoking individuals, stratified according to GPX1 rs1050450 and SEPP1 rs3877899 genotypes, and supplemented with selenium yeast (200 µg) for 6 weeks. Blood was collected at four time points, including 4 weeks of washout.ResultsAfter genotype stratification, the effect of GPX1 rs1050450 on lower GPx1 activity responsiveness was confirmed; however, in terms of DNA damage, we failed to indicate that individuals homozygous for variant allele may especially benefit from the increased selenium intake. Surprisingly, considering gene and time interaction, GPX1 polymorphism was observed to modify the level of DNA strand breaks during washout, showing a significant increase in GPX1 wild-type homozygotes. Regardless of the genotype, selenium supplementation was associated with a selectively suppressed selenoprotein mRNA expression and inconsistent changes in oxidative stress response, indicating for overlapped, antioxidant, and prooxidant effects. Intriguingly, DNA damage was not influenced by supplementation, but it was significantly increased during washout.ConclusionsThese results point to an unclear relationship between selenium, genotype, and DNA damage.Electronic supplementary materialThe online version of this article (doi:10.1007/s00394-015-1118-4) contains supplementary material, which is available to authorized users.