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Background  HIF-1 activates various genes in cancer progression and metastasis. HIF-1α 1772 C/T and 1790 G/A polymorphisms are reportedly associated with cancer risk; however, the results are inconclusive.    Methodology/Principal Findings  A meta-analysis of 34 studies that involved 7522 cases and 9847 controls for 1772 C/T and 24 studies that involved 4884 cases and 8154 controls for 1790 G/A was conducted to identify the association of C/T and G/A polymorphisms with cancer risk. Odds ratio (OR) and 95% confidence intervals (95% CI) were used to assess the strength of association.  HIF-1α 1772 C/T and 1790 G/A polymorphisms were associated with higher cancer risk in homozygote comparison (1772C/T: TT vs. CC: OR = 2.45, 95% CI: 1.52, 3.96;  P   heterogeneity  = 0.028; 1790G/A: AA vs. GG: OR=4.74, 95% CI: 1.78, 12.6;  P   heterogeneity  < 0.01), dominant model (1772C/T:  TT/CT  vs. CC: OR = 1.27, 95% CI: 1.04, 1.55;  P   heterogeneity  < 0.01, 1790G/A:  AA/GA  vs. GG: OR = 1.65, 95% CI: 1.05, 2.60;  P   heterogeneity  < 0.01), T allele versus C allele (T vs. C: OR = 1.42, 95% CI: 1.18, 1.70;  P   heterogeneity  < 0.01), and A allele versus G allele (A vs. G: OR = 1.83, 95% CI: 1.13, 2.96;  P   heterogeneity  < 0.01). On a subgroup analysis, the 1772 C/T polymorphism was significantly linked to higher risks for breast cancer, lung cancer, prostate cancer, and cervical cancer, whereas the 1790 G/A polymorphism was significantly linked to higher risks for lung cancer and prostate cancer. A significantly increased cancer risk was found in both Asians and Caucasians for 1772C/T polymorphism, whereas a significantly increased cancer risk was found in Caucasians in the heterozygote comparison and recessive model for 1790G/A polymorphism.    Conclusions  HIF-1α 1772 C/T and 1790 G/A polymorphisms are significantly associated with higher cancer risk.

HIF-1α 1772 C/T and 1790 G/A Polymorphisms Are Significantly Associated with Higher Cancer Risk: An Updated Meta-Analysis from 34 Case-Control Studies