Hypoxia-inducible factor-1α G polymorphism and the risk of cancer: a meta-analysis

Aims and background. Hypoxia-inducible factor-1 alpha (HIF-1 alpha), a transcription factor, is associated with the initiation and progression of malignant tumors. HIF-1 alpha G (A588T) polymorphism has been shown to lead to genetic susceptibility to malignant tumors but results have been controversial. Methods and study design. We carried out a meta-analysis on 21 eligible case-control studies with a total of 3892 cases and 6915 healthy controls to analyze the data with respect to the associations between HIF-1 alpha G polymorphism and the risk of cancer. The overall odds ratio (OR) with a 95% confidence interval (CI) were used to assess the association. Results. A statistically significant association between the HIF-1 alpha GA/AA genotype and cancer risk was found in the meta-analysis (OR, 1.79; 95% CI, 1.12-2.86; P-heterogeneity <0.00001). In the subgroup analysis by ethnicity, significantly increased cancer risks were revealed among European and East Asian populations for the GA/AA genotype compared to the GG genotype (OR, 3.54; 95% CI, 1.34-9.30; P-heterogeneity = 0.005; OR, 1.84; 95% CI, 1.06-3.17; P-heterogeneity = 0.001, respectively). In the subgroup analysis by different tumor types, GA/AA genotype markedly increased the risk of oral cancer and digestive system cancers (OR, 3.15; 95% CI, 1.05-9.47; Pheterogeneity = 0.004; OR, 2.20; 95% CI, 1.12-4.34; Pheterogeneity = 0.002; respectively). Moreover, no publication bias was shown, which was assessed by Begg's funnel plots. Conclusions. Our findings revealed that GA/AA genotype might be related to increased risks of oral cancer and digestive system cancers. Moreover, HIF-1 alpha G polymorphism might contribute to high susceptibility to malignant tumors, especially in European and East Asian populations.