Int J Cancer 2011 Jan;128(1):166-75
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.
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, p(corrected) = 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 (p(trend) = 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.