Hypoxia-Inducible Factor-1α Polymorphisms and Risk of Cancer Metastasis: A Meta-Analysis

BACKGROUND HIF-1α is a major regulator in tumor progression and metastasis which responds to hypoxia. Many studies have demonstrated that hypoxia-inducible factor1-α (HIF-1α) polymorphisms are significantly associated with cancer metastasis, but the results are inconsistent. We conducted a comprehensive meta-analysis to estimate the associations between HIF-1α C1772 T polymorphism and cancer metastasis. METHODS Comprehensive searches were conducted on PubMed and EMBASE database. Fifteen studies were included in the meta-analysis. We used the OR and 95%CI to assess the associations between HIF-1α C1772T polymorphism and cancer metastasis. Heterogeneity and publication bias were also assessed by Q test, I (2), and funnel plot. RESULTS Totally, fifteen studies including 1239 cases with metastasis-positive (M+) and 2711 cases with metastasis-negative (M-) were performed in this meta-analysis. The results showed that HIF-1a C1772T polymorphism was associated with the increased risk of cancer metastasis (T allele vs. C allele, OR  = 1.36, 95% CI  = 1.12-1.64; TT+ TC vs. CC, OR  = 1.39, 95% CI  = 1.13-1.71; TT vs. TC+ CC, OR  = 1.93, 95% CI  = 0.86-4.36). In the subgroup analyses, the significant associations remained significant among Asians, Caucasians and other cancers in the dominant model. Publication bias was not observed in the analysis. CONCLUSIONS Our results indicate that the HIF-1αC1772T polymorphism T allele may increase the risk of cancer metastasis, which might be a potential risk factor of cancer progress.