Association of VEGFA polymorphisms with susceptibility and clinical outcome of hepatocellular carcinoma in a Chinese Han population
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Fei Liu1,*, Limei Luo2,*, Yonggang Wei1, Wentao Wang1, Tianfu Wen1, Jiayin Yang1, Mingqing Xu1, Bo Li1
1Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
2Department of Clinical Immunological Laboratory, West China Hospital, Sichuan University, 610041, China
*These authors contributed equally to this work
Bo Li, email: firstname.lastname@example.org
Yonggang Wei, email: email@example.com
Keywords: hepatocellular carcinoma, VEGFA, polymorphism, susceptibility, clinical outcome
Received: September 06, 2016 Accepted: January 16, 2017 Published: January 27, 2017
Vascular endothelial growth factor A (VEGFA) is an important angiogenesis regulator, which plays an important role in angiogenesis and progression of tumor, including hepatocellular carcinoma (HCC). We aimed at determining whether single nucleotide polymorphisms of VEGFA gene influence the development and clinical outcomes of HCC. We analyzed four potential functional polymorphisms (936C/T, 634G/C, 1612G/A, 2578C/A) of VEGFA gene in 476 HCC patients and 526 controls using matrix-assisted laser desorption ionization time-of-flight mass spectrometry method. Serum VEGF levels were measured by enzyme-linked immunosorbent assay. The Kaplan-Meier methods with log-rank test and Cox regression models were used to compare survival of resected HCC patients according to the genotype. We found that only the VEGFA 2578C/A polymorphism was significantly associated with decreased risk of HCC (AA/AC vs. CC; adjusted OR = 0.69, 95% CI = 0.51−0.93). Furthermore, the 2578C/A polymorphism was associated with significantly decreased postoperative recurrence (AA/AC vs. CC, adjusted OR = 0.51; 95% CI, 0.29−0.88) and improved overall survival (AA/AC vs. CC, adjusted HR = 0.27, 95% CI = 0.13−0.52) of resected HCC patients. In addition, the VEGF serum levels in HCC patients were significantly higher than those in healthy controls, although no significant association between VEGFA genotype and serum levels of VEGF was observed. These results suggest that the VEGFA 2578 C/A polymorphism may play a potential role in the development and clinical outcome of HCC among Chinese Han population.
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