Clinicopathological significance of hypoxia-inducible factor-1 alpha polymorphisms in cancers: evidence from a meta-analysis

The associations between hypoxia-inducible factor-1 alpha (HIF-1α) and clinicopathological characteristics of cancers have been evaluated in various studies, with the conflicting results. Therefore, we conducted a meta-analysis by combining available data to derive a more precise estimation of the association. PubMed, Embase, and China National Knowledge Infrastructure (CNKI) were searched until February 2013 to identify eligible studies. A total of 25 studies were included, with all studies investigating the role of HIF-1α C1772T polymorphism in clinicopathological parameters in cancers while 17 of them investigating HIF-1α G1790A polymorphism only. Results suggested that HIF-1α C1772T polymorphism was associated with histological grade of cancer (T/T + C/T vs. C/C, grade 3 vs. grade 2: OR = 1.51, 95% CI = 1.08-2.13; grade 2 vs. grade 1: OR = 0.67, 95% CI = 0.46-0.97) and increased risk of lymph node metastasis (T/T + C/T vs. C/C: OR = 1.38, 95% CI = 1.13-1.68). HIF-1α G1790A polymorphism was found to be associated with increased risk of larger tumor size (G/G + G/A vs. A/A: OR = 1.64, 95% CI = 1.04-2.58) and borderline significant risk of lymph node metastasis (G/G + G/A vs. A/A: OR = 1.33, 95% CI = 1.00-1.78). Therefore, HIF-1α polymorphisms could be a potential prognostic factor for cancer. Further studies with larger data set and well-designed models are required to validate our findings.