摘要
Purpose
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.
摘要译文
目的NRF2转录因子参与的各种抗氧化和代谢的基因的调制，因此，可以调节抗致癌潜能。NRF2基因多态性和五个NRF2调节基因和膀胱癌（BC）的风险之间的关联进行了分析。方法研究组包括244 BC患者，而对照组由365个人有没有证据恶性肿瘤。 GSTM1（删除），GSTT1（删除）的基因分型，GSTA1SOD2 Ala16Val（rs4880）和NRF2基因多态性与BC风险之间的关联是由logistic回归计算。结果GSTA1，GSTP1，SOD2和NRF2基因型频率两组没有显着差异。一个显著高于BC风险与GSTM1空白基因型相关调整年龄，性别和吸烟习惯后（OR 1.85，95％CI 1.30-2.62; P \x3d 0.001）。 GSTT1空（OR 0.50，95％CI 0.31-0.81;P \x3d 0.005）和GSTP1 Val105Val（OR 0.52，95％CI 0.27-0.98; P \x3d 0.04）基因型与BC减少单独或组合（OR 0.24的风险，95％CI 0.11-0.51相关; P0001）（P异质\x3d 0.01）。联合GSTT1零和SOD2与不吸烟者中的至少一个等位基因16Val包括降低风险的BC（OR 0.14，95％CI 0.03-0.63; P \x3d 0.01）（P \x3d异质0。04）。结论：这项研究支持假说，即GSTM1空白基因型可能是一个温和的BC危险因素。ND与GSTP1结合/ GSTT1相关，并结合GSTT1 / SOD2随着吸烟习惯的遗传多态性基因与环境的相互作用可能在BC风险调制显著的作用。
Edyta Reszka [1] Zbigniew Jablonowski [2] Edyta Wieczorek [1] Ewa Jablonska [1] Magdalena Beata Krol [1] Jolanta Gromadzinska [1] Adam Grzegorczyk [2] Marek Sosnowski [2] Wojciech Wasowicz [1]. Polymorphisms of NRF2 and NRF2 target genes in urinary bladder cancer patients[J]. Journal of Cancer Research and Clinical Oncology, 2014,140(10): 1723-1731