Possible association between polymorphisms of human vascular endothelial growth factor A gene and susceptibility to glioma in a Chinese population

Authors

  • Rui Li,

    1. State Key Laboratory of Genetic Engineering, Center for Fudan-VARI Genetics Epidemiology and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China
    Search for more papers by this author
    • Rui Li and Yao Zhao contributed equally to this work.

  • Yao Zhao,

    1. Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China
    Search for more papers by this author
    • Rui Li and Yao Zhao contributed equally to this work.

  • Weiwei Fan,

    1. State Key Laboratory of Genetic Engineering, Center for Fudan-VARI Genetics Epidemiology and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China
    Search for more papers by this author
  • Hongyan Chen,

    1. State Key Laboratory of Genetic Engineering, Center for Fudan-VARI Genetics Epidemiology and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China
    Search for more papers by this author
  • Yuanyuan Chen,

    1. State Key Laboratory of Genetic Engineering, Center for Fudan-VARI Genetics Epidemiology and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China
    Search for more papers by this author
  • Yanhong Liu,

    1. State Key Laboratory of Genetic Engineering, Center for Fudan-VARI Genetics Epidemiology and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China
    2. Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, TX
    Search for more papers by this author
  • Gong Chen,

    1. Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China
    Search for more papers by this author
  • Keke Zhou,

    1. Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China
    Search for more papers by this author
  • Fengping Huang,

    1. Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China
    Search for more papers by this author
  • Ying Mao,

    Corresponding author
    1. Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China
    • Neurosurgery Department of Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai 200040, China
    Search for more papers by this author
    • Tel.: +8621-62489999 ext. 420

  • Liangfu Zhou,

    1. Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China
    Search for more papers by this author
  • Daru Lu,

    Corresponding author
    1. State Key Laboratory of Genetic Engineering, Center for Fudan-VARI Genetics Epidemiology and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China
    • State Key Laboratory of Genetic Engineering, Center for Fudan-VARI Genetics Epidemiology and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, 220 Handan Road, Shanghai 200433, China
    Search for more papers by this author
    • Tel.: 8621-65642799

  • Yin Yao Shugart

    1. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
    2. Genomic Research Branch, Division of Neuroscience and Basic Behavioral Science, National Institute of Mental Health, National Institutes of Health, Bethesda, MD
    Search for more papers by this author

Abstract

Vascular endothelial growth factor A (VEGFA), one of the most predominant mediators of pathologic angiogenesis, plays a critical role in glioma carcinogenesis and development via promoting tumor growth. We hypothesized that VEGFA polymorphisms may influence glioma risk. We recently genotyped 9 VEGFA single-nucleotide polymorphisms (SNPs) in 766 glioma patients and 824 cancer-free controls selected from a Chinese population. We evaluated the glioma risk conferred by individual SNPs, haplotypes as well as cumulative SNP effect. In the single-locus analysis, we found that rs2010963 (G+405C, G-634C) [odds ratio (OR) = 1.29; 95% confidence interval (CI) = 1.04–1.58; GC/CC vs. GG] and rs3025030 (OR = 2.21; 95% CI = 1.18–4.14; CC vs. GG/GC) were associated with increased risk for glioma, and rs3024994 (OR = 0.66; 95% CI = 0.47–0.94; CT/TT vs. CC) was associated with reduced glioma risk, albeit insignificant after Bonferroni correction for multiple comparisons. The haplotype-based analysis revealed that AGG in block 1 and ATT, ACT in block 2 were associated with 20–40% reductions in glioma risk. The inverse association of haplotype AGG containing rs2010963G remained significant after correction for multiple testing (p = 0.002, pcorrected = 0.022). The aforementioned 3 SNPs revealed a significant cumulative risk effect; the increased risk for glioma was 1.38-fold for each additional adverse genotype he or she carries (ptrend = 8.4 × 10−5). Our findings suggested that VEGFA variants may be involved in glioma risk. Larger studies with ethnically diverse populations are warranted to confirm the results reported in this investigation.

Ancillary