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KMID : 1001020030010040358
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Korean Journal of Urological Oncology
2003 Volume.1 No. 4 p.358 ~ p.364
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Polymorphisms of TGF-β1 and VEGF Gene Promoter Regions in Bladder Tumor
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Kim Tae-Hwan
Kim Wun-Jae
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Abstract
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Purpose: VEGF is a strong angiogenic factor and TGF-β1 is a multifunctional cytokine which regulate the tumor development and suppression. Therefore, we investigated whether the genetic polymorphisms of promoter regions in VEGF and TGF-β1 had the effects on the bladder tumor development, progression and recurrence.
Materials and Methods: Hospital based, case-control investigation was carried out in 162 primary bladder tumor patients and 172 controls subjects. We performed the PCR-based restriction fragment length polymorphism (RFLP) and direct DNA sequencing to characterize the genetic polymorphisms of TGF-β1 ?509 and VEGF ?2578 regions in both cases and controls. Also genotypes of TGF-β1 ?509 and VEGF ?2578 regions in bladder tumor tissues associated with clinical findings were investigated.
Results: We found that the genotype of TGF-β1 ?509 region in controls(CC, 26.7%; CT, 54.7%; TT, 18.6%) was significantly different from that of bladder tumor patients(14.8%, 67.3% and 17.9%, respectively)(p=0.019). The risk for bladder tumor in CT(p=0.005; OR=0.45; CI=0.256-0.792) and CT?TT types(p=0.007; OR=0.476; CI=0.275-0.825) were approximately 2 times higher compared with CC type. Especially the risk of invasive bladder tumor in CT?TT types(p=0.040; OR=2.556; CI=1.019-6.410) were approximately 2.5 times higher than CC type. The genotype of VEGF ?2578 region(CC, CA and AA type) was not different between bladder tumor patients and controls. But the higher was the grade in bladder tumor, the more frequent was the AA type of VEGF ?2578 region compared to CC type(p=0.020; OR=5.113; CI=1.175-22.258). In bladder tumor tissues the frequency of TGF-β1 ?509 TT type was significantly higher than CT type(p=0.037; OR=2.932; CI=1.045-8.226) and CC?CT types(p=0.036; OR=2.845; CI=1.045-7.743). And the higher was the grade in bladder tumor, the more frequent was the TT type of TGF-β1 ?509 region compared to CC?CT types. Only AA genotype of VEGF ?2578 region in bladder tumor tissues was observed in grade III.
Conclusions: These data suggested that genotypes of TGF-β1 ?509 and VEGF ?2578 regions might involve the tumorigenesis of the urinary bladder and have the effects on the aggressiveness of human bladder tumors.
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KEYWORD
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VEGF, TGF-β1, Promoter, Genetic polymorphism, Bladder tumor
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