Associations of single nucleotide polymorphisms in the vascular endothelial growth factor gene with the characteristics and prognosis of renal cell carcinomas.
OBJECTIVE
Vascular endothelial growth factor (VEGF) is considered to play critical roles in tumor development and progression, especially in renal cell carcinoma (RCC) via von Hippel-Lindau gene inactivation. Although VEGF -2578CC, -1154GG, and -634CC genotypes are reportedly correlated with higher levels of VEGF production, no previous studies have reported on the associations of these polymorphisms with RCCs. This study was aimed to clarify the effects of these functional polymorphisms on RCC progression and prognosis.


METHODS
We investigated the associations of three polymorphisms (-2578C/A, -1154G/A, and -634C/G) in the VEGF gene with the clinicopathologic parameters and survival of 213 patients with RCC. The -2578C/A and -634C/G polymorphisms were genotyped using a polymerase chain reaction (PCR) restriction fragment length polymorphism technique and the -1154G/A polymorphism was genotyped by an amplification refractory mutation system PCR technique.


RESULTS
The GA+AA genotypes of -1154G/A were weakly associated with smaller tumors, lower tumor stage, and lower stage grouping (p=0.028, p=0.012, and p=0.028, respectively). The CA and CA+AA genotypes of -2578C/A were weakly associated with less frequent lymph node metastasis (p=0.029 and p=0.034, respectively) and were significantly associated with favorable cancer-specific survival (p=0.047 and p=0.048, respectively). There was no apparent clinical effect of the -634C/G polymorphism.


CONCLUSIONS
These results suggest that some VEGF genotypes may have effects on RCC progression or prognosis, possibly through altered VEGF expression. This finding might help in clarifying the mechanisms of RCC development and progression.
Kawai
Yoshihisa
Y
Department of Urology, Yamaguchi University School of Medicine, Yamaguchi, Japan.
Sakano
Shigeru
S
Korenaga
Yoshihito
Y
Eguchi
Satoshi
S
Naito
Katsusuke
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005838:Genotype; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D017931:DNA Primers; D004273:DNA, Neoplasm; D042461:Vascular Endothelial Growth Factor A