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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.

SUBMITTER: Liu F

PROVIDER: S-EPMC5369979 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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

Liu Fei F Luo Limei L Wei Yonggang Y Wang Wentao W Wen Tianfu T Yang Jiayin J Xu Mingqing M Li Bo B

Oncotarget 20170301 10

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 d ...[more]

PMID: 28147320

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Project description:BACKGROUND Hepatocellular carcinoma (HCC) is one of the most common types of liver cancer. It is hypothesized that P2RX7 genetic polymorphisms have strong association with HCC susceptibility. Therefore, a case-control study was designed and performed to verify the association between P2RX7 gene polymorphisms and HCC susceptibility. MATERIAL AND METHODS A total of 646 subjects were recruited in our study, including 323 HCC patients and 323 healthy controls. Five gene polymorphisms, -762C>T (rs2393799), 946G>A (rs28360457), 1513A>C (rs3751143), 1068G>A (rs1718119), and 1096C>G (rs2230911), were selected. Odds ratio (ORs) and 95% confidence interval (CI) were used to quantify the association between P2RX7 gene polymorphisms and the susceptibility to HCC. All tests were performed using SPSS 20 and a 2-sided P value of less than 0.05 was considered to be statistically significant. RESULTS Our results suggest that allelic frequencies of these 5 SNPs all conformed to Hardy-Weinberg equilibrium (HWE). There was no significant difference in genotype and allele distributions of -762C>T and 1096C>G between the case group and the control group. However, an increased risk of HCC was associated with 946G>A (A vs. G: OR=1.48, 95%CI=1.09-2.01, P=0.013; GA+AA vs. GG: OR=1.46, 95%CI=1.03-2.07, P=0.033). A similar increased risk was associated with 1513A>C polymorphism (C vs. A: OR=1.37, 95%CI=1.05-1.79, P=0.021; AC+CC vs. AA: OR=1.40, 95%CI=1.01-1.93, P=0.041). On the other hand, a decreased risk of HCC was associated with gene polymorphism of 1068G>A (A vs. G: OR=0.68, 95%CI=0.51-0.91, P=0.010; GA+AA vs. GG: OR=0.68, 95%CI=0.49-0.96, P=0.027; AA vs. GG: OR=0.42, 95%CI=0.18-0.99, P=0.048). CONCLUSIONS Our results suggest that 3 of the 5 polymorphisms of P2RX7 described above (1513A>C, 946G>A, and 1068G>A) are significantly associated with HCC susceptibility in a Chinese Han population. Studies with larger sample sizes are recommended to confirm whether our results will be applicable to different ethnic populations in China.

Project description:BackgroundThe identification of susceptibility genes for specific types of cancer can provide necessary information for the complete characterization of cancer syndromes. Eight single nucleotide polymorphisms (SNPs), rs465498, rs17728461, rs4488809, rs753955, rs13361707, rs9841504, rs2274223, and rs13042395, were reported by genome wide association studies (GWASs) to be closely related to the susceptibility of lung cancer (LC), gastric cancer (GC) or esophageal cancer (EC) in Han population from northern or southern China. However, Chinese Han people from different geographic areas may have different genetic backgrounds. This study aims to assess the genetic associations of the eight SNPs mentioned above with three cancers risk in a Han population from northwest China.MethodsA total of 186 cancer-free controls and 436 cases with non-small cell lung cancer (NSCLC) (159 cases), non-cardia GC (167 cases) or EC (110 cases) were enrolled in this study. Chi-square test and polytomous logistic regression analyses were used to estimate the association between eight cancer-related SNPs and three cancers in a Han Chinese population from northwest China. The logistic regression results were adjusted for confounding factors and Benjamini and Hochberg False Discovery Rate (FDR) method was used to adjust the multiple hypothesis tests. Association analyses by cigarette smoking or alcohol drinking status were analyzed by crossover analyses.ResultsOne of the eight SNPs, rs17728461 was associated with NSCLC susceptibility (in a heterozygous model, OR = 0.44, 95% CI = 0.27-0.72, p = 0.001). Two SNPs, rs753955 and rs13042395, were associated with the risk of non-cardia GC in different genetic models (p < 0.05). No SNPs were associated with EC. The crossover analyses showed that the rs13042395 CT genotype, combined with cigarette smoking or alcohol drinking, could further increase the risk for non-cardia GC (p < 0.05).ConclusionsThese results indicated that rs17728461 may be specifically associated with the risk of NSCLC. rs753955 and rs13042395 were specifically associated with susceptibility to non-cardia GC in Ningxia Han Chinese. Susceptibility-associated polymorphisms in the northwestern Han Chinese were not very consistent with those in the northern Han Chinese or southern Han Chinese. The validation of these findings with a functional evaluation and a larger population is still required.

Dataset Information

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

Publications

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

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