Association between vascular endothelial growth factor gene polymorphisms and survival in hepatocellular carcinoma patients.
Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis and progression of tumor, including hepatocellular carcinoma (HCC), and elevated VEGF levels in serum and tissues have been known to be related with poor prognosis in patients with HCC. However, the effect of such polymorphisms of the VEGF gene on HCC prognosis has not been elucidated. In the present study, we investigated the association between VEGF gene polymorphisms and HCC patient prognosis. The study involved 416 HCC patients treated at the National Cancer Center Korea from November 2000 to December 2005. The median patient age was 57 years, and 328 patients (78.8%) were men. A total of 19 polymorphisms were analyzed, and the hazard ratios (HRs) for genotypes and haplotypes were determined in terms of risk for overall survival using Cox proportional hazard regression analysis. Of the 19 alleles, 7 showed no heterozygous allele. PHASE analysis identified a total of 36 haplotypes. The -2578 to -1498 region of the VEGF gene showed a strong linkage disequilibrium (correlation coefficient, r(2) = 0.91; Lewontin's D', D' = 0.982). The adjusted HRs were 0.67 [95% confidence interval (CI), 0.46 to 0.99] for -634CC genotype carriers and 0.57 (95% CI, 0.36 to 0.92) for homozygous haplotype 1 (Ht1: CCGAGCCC at -2578/-1203/-1190/-1179/-1154/-634/-7/+936) carriers compared with noncarriers.


CONCLUSIONS
These findings suggest that VEGF polymorphisms may be significant prognostic indicators for HCC patients.
Center for Clinical Services, Department of Laboratory Medicine, Research Institute and Hospital, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea.
Sun-Young
SY
Kong
Joong-Won
JW
Park
Jung An
JA
Lee
Jung Eun
JE
Park
Kyung Woo
KW
Park
Eun Kyung
EK
Hong
Chang-Min
CM
Kim
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000235:genetics*
D042461:Vascular Endothelial Growth Factor A