Polymorphisms of NRF2 and NRF2 target genes in urinary bladder cancer patients

Reszka, Edyta; Jabłonowski, Zbigniew; Wieczorek, Edyta; Jabłońska, Ewa; Król, Magdalena Beata; Gromadzińska, Jolanta; Grzegorczyk, Adam; Sosnowski, Marek; Wąsowicz, Wojciech

doi:10.1007/s00432-014-1733-0

Cited by 31 publications

(26 citation statements)

References 51 publications

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“…The transaldolase gene, TALDO1 , is activated by NF-E2 related factor 2 (Nrf2), a ubiquitous transcription factor with a major role in cytoprotection [ 34 ]. Nrf2 has been extensively studied in bladder as a defender against tobacco carcinogens [ 35 , 36 ]; conversely, Nrf2 may also protect bladder cancer cells against reactive oxygen species and promote resistance to chemotherapeutic agents [ 37 , 38 ]. When redox balance is disturbed, Nrf2 translocates to the nucleus and activates the antioxidant response elements (ARE) of several genes with antioxidant functions [ 39 ] including TALDO1 [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Characterization of urinary extracellular vesicle proteins in muscle-invasive bladder cancer

et al. 2017

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The mechanisms of bladder cancer progression are unknown, and new treatments and biomarkers are needed. Patient urinary extracellular vesicles (EVs) derive in part from bladder cancer cells and contain a specific protein cargo which may provide information about the disease. We conducted a proteomics study comparing EVs from the muscle-invasive bladder cancer (MIBC) cell line TCCSUP to EVs from normal urothelial line SVHUC. GO term analysis showed that TCCSUP EVs are enriched in proteins associated with the cell membrane, extracellular matrix, and inflammation and angiogenesis signaling pathways. Proteins characteristic of cancer EVs were further screened at the mRNA level in bladder cancer cell lines. In Western blots, three of six proteins examined showed greater than fifteenfold enrichment in patient urinary EVs compared to healthy volunteers (n = 6). Finally, we performed immunohistochemical staining of bladder tissue microarrays for three proteins of interest. One of them, transaldolase (TALDO1), is a nearly ubiquitous enzyme and normally thought to reside in the cytoplasm. To our surprise, nuclei were stained for transaldolase in 94% of MIBC tissue samples (n = 51). While cytoplasmic transaldolase was found in 89-90% of both normal urothelium (n = 79) and non-muscle-invasive samples (n = 71), the rate falls to 39% in MIBC samples (P < 0.001), and negative cytoplasmic staining was correlated with worse cancer-specific survival in MIBC patients (P = 0.008). The differential EV proteomics strategy reported here successfully identified a number of proteins associated with bladder cancer and points the way to future investigation.

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Section: Discussionmentioning

confidence: 99%

Characterization of urinary extracellular vesicle proteins in muscle-invasive bladder cancer

et al. 2017

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“…Regardless of the tumor type Nrf2 expression is elevated in head and neck, bladder, colorectal, and lung tumors (47-50). Furthermore, the minor allele of rs6721961 SNP has not been associated with bladder, lung, gastric or colorectal carcinogenesis (48). …”

Section: Discussionmentioning

confidence: 99%

A Preliminary Study on Racial Differences in HMOX1, NFE2L2, and TGFβ1 Gene Polymorphisms and Radiation-Induced Late Normal Tissue Toxicity

Alam

Mukhopadhyay

Ning

et al. 2015

International Journal of Radiation Oncology*Biology*Physics

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Purpose This study tests whether racial differences in genetic polymorphisms of four genes involved in wound repair and response to radiation can be used to predict the occurrence of normal tissue late effects of radiotherapy and indicate potential therapeutic targets. Methods and Materials This prospective study examines genetic polymorphisms that modulate the expression of four genes involved in inflammation and fibrosis and response to radiation (HMOX1, NFE2L2, NOS3 and TGFβ1). DNA from blood samples of 179 patients (~80% breast and head and neck) collected at the time of diagnosis by their radiation oncologist as exhibiting late normal tissue toxicity was used for the analysis. Patient demographics were: 56% Caucasian, 43% African-American, 1% other. Allelic frequencies of the different polymorphisms of the participants were compared to those of the general American population stratified by race. Twenty-six additional patients treated with radiation, but without toxicity at 3 months or later post-therapy, were also analyzed. Results Increased frequency of a long GT repeat in the HMOX1 promoter was associated with late effects in both African-American and Caucasian populations. The single nucleotide polymorphisms (SNP) rs1800469 in the TGFβ1 promoter and the rs6721961 SNP in the NFE2L2 promoter were also found to significantly associate with late effects in African-Americans but not Caucasians. A combined analysis of these polymorphisms revealed that >90% of African-American patients with late effects had at least one and 58% two or more of these minor alleles. No statistical significance was found relating the studied NOS3 polymorphisms and normal tissue toxicity. Conclusions These results support a strong association between wound repair and late toxicities of radiation. The presence of these genetic risk factors can vary significantly among different ethnic groups, as demonstrated for some of the SNPs. Future studies should account for the possibility of such ethnic heterogeneity in the late toxicities of radiation.

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“…In the subgroup of patients and controls who smoked cigarettes, we included 24 studies [ 25 , 30 , 34 , 35 , 42 , 43 , 47 , 48 , 50 , 51 , 54 – 56 , 64 , 65 , 68 , 69 , 73 , 76 , 83 , 85 , 91 , 92 , 95 ] (data not shown) containing 3724 case series and 3160 controls. Average distribution frequency of the GSTM1-null genotype was 55.67% in the bladder cancer group and 47.57% in the control group, indicating that the GSTM1-null genotype was significantly higher in the bladder cancer cases compared with the controls (case/control = 1.17).…”

Section: Resultsmentioning

confidence: 99%

Association of Glutathione S-transferase gene polymorphism with bladder Cancer susceptibility

Zhou

Xie

et al. 2018

BMC Cancer

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BackgroundWe conducted a meta-analysis to evaluate the relationship between the glutathione S-transferase μ1 (GSTM1)– and glutathione S-transferase θ1 (GSTT1)– null genotypes and susceptibility to bladder cancer.MethodsWe identified association reports from the databases of PubMed, Embase, the Cochrane Library and the China Biological Medicine Database (CBM disc) on July 1, 2017 and synthesized eligible investigations. Results were expressed using odds ratios (ORs) for dichotomous data, and we also calculated 95% confidence intervals (CIs).ResultsIn this meta-analysis, we found that the GSTM1-null genotype was associated with bladder cancer risk in the overall population, and individually in whites, Africans and Asians (overall population: OR = 1.40, 95% CI: 1.31–1.48, P<0.00001; whites: OR = 1.39, 95% CI: 1.26–1.54, P<0.00001; Africans: OR = 1.54, 95% CI: 1.16–2.05, P = 0.003; Asians: OR = 1.45, 95% CI: 1.33–1.59, P<0.00001). The GSTT1-null genotype was associated with bladder cancer risk in the overall population, but not in whites, in Africans or Asians (overall population: OR = 1.11, 95% CI: 1.01–1.22, P = 0.03; whites: OR = 1.16, 95% CI: 0.99–1.36, P = 0.07; Africans: OR = 1.07, 95% CI: 0.65–1.76, P = 0.79; Asians: OR = 1.05, 95% CI: 0.91–1.22, P = 0.51). Interestingly, a dual-null GSTM1–GSTT1 genotype was associated with bladder cancer risk in the overall population and in Asians (overall population: OR = 1.48, 95% CI: 1.15–1.92, P = 0.002; Asians: OR = 1.62, 95% CI: 1.15–2.28, P = 0.006). In conclusion, the GSTM1-null, GSTT1-null and dual-null GSTM1–GSTT1 genotypes might be associated with the onset of bladder cancer, but additional genetic-epidemiological studies should be conducted to explore this association further.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-5014-1) contains supplementary material, which is available to authorized users.

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Polymorphisms of NRF2 and NRF2 target genes in urinary bladder cancer patients

Cited by 31 publications

References 51 publications

Characterization of urinary extracellular vesicle proteins in muscle-invasive bladder cancer

Characterization of urinary extracellular vesicle proteins in muscle-invasive bladder cancer

A Preliminary Study on Racial Differences in HMOX1, NFE2L2, and TGFβ1 Gene Polymorphisms and Radiation-Induced Late Normal Tissue Toxicity

Association of Glutathione S-transferase gene polymorphism with bladder Cancer susceptibility

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