Genotypes of TNF-alpha, VEGF, hOGG1, GSTM1, and GSTT1: useful determinants for clinical outcome of bladder cancer.
OBJECTIVE
To determine whether polymorphisms of tumor necrosis factor-alpha (TNF-alpha), vascular endothelial growth factor (VEGF), human 8-oxoguanine DNA glycosylase 1 (hOGG1), glutathione S-transferase-mu (GSTM1), and glutathione S-transferase-phi (GSTT1) are risk factors for bladder cancer among Koreans.


METHODS
We performed polymerase chain reaction-restriction fragment length polymorphism and multiplex polymerase chain reaction in blood genomic DNA of 153 patients with primary bladder cancer and 153 control subjects.


RESULTS
GSTM1-negative, GSTT1-positive, and hOGG1 Ser326Ser and Ser326Cys genotypes are risk factors for bladder cancer (P = 0.020, P = 0.044, and P = 0.012, respectively). The cancer stage was significantly associated with the TNF-alpha genotype (GG versus GA and AA; P = 0.036). A notable correlation was observed between the VEGF genotype and grade (P = 0.015). In patients with superficial bladder cancer, the hOGG1 genotype was related to recurrence. The hOGG1 Ser326Ser and Ser326Cys genotypes were risk factors for superficial bladder cancer recurrence compared with the Cys326Cys genotype (P = 0.033, adjusted odds ratio 5.580, 95% confidence interval 1.145 to 27.183). Patients with the GSTM1-positive genotype were at a 3.3-fold increased risk of cancer progression compared with those with the GSTM1-negative genotype (P = 0.009, adjusted odds ratio 0.303, 95% confidence interval 0.123 to 0.745).


CONCLUSIONS
Our data collectively suggest that these genetic polymorphisms may be useful as prognostic markers for bladder cancer in the clinical setting.
Kim
Eun-Jung
EJ
Department of Urology, Chungbuk National University College of Medicine, Cheongju, Chungbuk, South Korea.
Jeong
Pildu
P
Quan
Changyi
C
Kim
Jiyeon
J
Bae
Suk-Chul
SC
Yoon
Seok Jung
SJ
Kang
Jong-Won
JW
Lee
Sang-Cheol
SC
Jun Wee
Jae
J
Kim
Wun-Jae
WJ
D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D002295:Carcinoma, Transitional Cell / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D045647:DNA Glycosylases / Q000032:analysis / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000032:analysis / Q000235:genetics*; D006801:Humans; D007723:Korea / Q000453:epidemiology; D008297:Male; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000235:genetics*
D014408:Biomarkers, Tumor; D045647:DNA Glycosylases; D005982:Glutathione Transferase; D009363:Neoplasm Proteins; D042461:Vascular Endothelial Growth Factor A; C467484:VEGFA protein, human; C479058:oxoguanine glycosylase 1, human