title: Polymorphisms of NRF2 and NRF2 target genes in urinary bladder cancer patients.
abstract: OBJECTIVE
  NRF2 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.
  
  
  METHODS
  The 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.
  
  
  RESULTS
  The 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).
  
  
  CONCLUSIONS
  This 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.
authors.affiliation: Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Teresy St. 8, 91-348, Lodz, Poland, edyta@imp.lodz.pl.
authors.forename: Edyta
authors.initials: E
authors.lastname: Reszka
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Jablonowski
authors.forename: Edyta
authors.initials: E
authors.lastname: Wieczorek
authors.forename: Ewa
authors.initials: E
authors.lastname: Jablonska
authors.forename: Magdalena Beata
authors.initials: MB
authors.lastname: Krol
authors.forename: Jolanta
authors.initials: J
authors.lastname: Gromadzinska
authors.forename: Adam
authors.initials: A
authors.lastname: Grzegorczyk
authors.forename: Marek
authors.initials: M
authors.lastname: Sosnowski
authors.forename: Wojciech
authors.initials: W
authors.lastname: Wasowicz
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000409:Alanine; D004843:Epistasis, Genetic; D005260:Female; D017353:Gene Deletion; D059647:Gene-Environment Interaction; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007532:Isoleucine; D008297:Male; D008875:Middle Aged; D051267:NF-E2-Related Factor 2 / Q000235:genetics*; D060787:Neoplasm Grading; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects; D013482:Superoxide Dismutase / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D014633:Valine; D000099156:Superoxide Dismutase 2
chemical_list: D000409:Alanine; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D007532:Isoleucine; D051267:NF-E2-Related Factor 2; D013482:Superoxide Dismutase; D014633:Valine; D000099156:Superoxide Dismutase 2; C495635:NFE2L2 protein, human; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human