Association of VEGFA polymorphisms with susceptibility and clinical outcome of hepatocellular carcinoma in a Chinese Han population

Abstract

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.

Haplotype‐based association of Vascular Endothelial Growth Factor gene polymorphisms with urothelial bladder cancer risk in Tunisian population

“…Different studies showed that associations were variables and differed according to tumor type. Data from case‐control studies revealed similar results with cervical cancer (OR (95% CI), 0.39 (0.16‐0.96), P = .040), prostate cancer (OR (95% CI), 0.16 (0.04‐0.70), P = .007) and hepatocellular carcinoma (OR (95% CI), 0.51 (0.28, 0.92), P = .024) . Mishra et al also found that CA genotype was associated with decreased risk of Gallbladder cancer risk.…”

“…Data from case-control studies revealed similar results with cervical cancer (OR (95% CI), 0.39 (0.16-0.96), P = .040), 16 prostate cancer (OR (95% CI), 0.16 (0.04-0.70), P = .007) 17 and hepatocellular carcinoma (OR (95% CI), 0.51 (0.28, 0.92), P = .024). 18 Mishra et al 19 also found that CA genotype was associated with decreased risk of Gallbladder cancer risk. In another case-control study, a significant association was observed with carriers of CC genotype in patients with increased nasopharyngeal cancer risk in Tunisian 20 and with invasive breast cancer in an American cohort (OR (95% CI), 1.46 (1.00-2.14), P = .049).…”

Clinical significance and prospective molecular mechanism of MALAT1 in pancreatic cancer exploration: a comprehensive study based on the GeneChip, GEO, Oncomine, and TCGA databases

“…Upregulated VEGFA is common in many tumors and is related to tumor stage and progression. Liu et al 64 reported that VEGFA polymorphisms might play a potential role in the development and clinical outcome of hepatocellular carcinoma. VEGFA has also been found to be inhibited by miR-1, which exerts inhibitory functions in osteosarcoma cells, as well as promotes proliferation, migration, and invasion.…”

Dandelion Polysaccharide Exerts Anti-Angiogenesis Effect on Hepatocellular Carcinoma by Regulating VEGF/HIF-1α Expression

“…Vascular endothelial growth factor (VEGF), one of the most prominent regulators involving vasculogenesis, is highly expressed in human HCC specimens (Choi et al, 2017;Liu et al, 2017). Hypoxia is one of the most potent stimuli for increased VEGF production in tumor cells (Liu et al, 2017;Campbell et al, 2019). With tumor tissues growing, one of the critical mediators of hypoxic responses is the hypoxia-inducible factor 1a (HIF-1a).…”