Breast cancer (BC) is considered to be one of the most malignant diseases. The microenvironment of BC is characterized as a hypoxic-like environment. Hypoxia inducible factor (HIF) is activated during hypoxic conditions, which can be generated by the BC microenvironment. Previous studies showed the relation between HIF genetic variations and BC, but were not well characterized. The objective of this meta-analysis is to analyze the relation of the HIF1A C1772T with BC by reviewing and analyzing established studies. All the data was gathered from nine studies that focused on HIF1A C1772T and BC. The literature was retrieved from electronic databases such as Web of Science, PubMed and Embase. All of the statistical data was subjected to either a fixed or random effects model to calculate OR and 95% confidence interval of pooled studies. The data was then analyzed by using the MetaGenyo web tool. This study did not find evidence for publication bias. The outcomes of the present study showed that HIF1A gene C1772T variant is not correlated with the risk of BC. However, sub-group studies by origin implied that the probability of BC was both strongly correlated with the HIF1A C1772T variant and significantly elevated among Asians. In summary, this study suggests that the probability of BC associated with the HIF1A C1772T variant was significantly higher in Asians compared to Caucasians.

Expression of hypoxia-inducible factors (HIFs) and N-myc downstream-regulated gene 3 (NDRG3) are oxygen-dependently regulated by prolyl hydroxylase domain (PHD) enzymes. Little is known about the role of NDRG3 in the cellular adaptation to hypoxia, whereas the roles of HIFs are well understood. In this study, we investigated how NDRG3 affects the hypoxic response in prostate cancer cells. Compared with HIF-1 alpha, hypoxic induction of NDRG3 was observed at a later phase. NDRG3 reduced hypoxic expression of HIF-1 alpha by inhibiting AKT-driven translation of HIF1A mRNA. In addition, NDRG3 functionally inhibited HIF-1 by dissociating the coactivator p300 from HIF-1 alpha. Accordingly, NDRG3 may fine-tune the HIF-1 signaling pathway to cope with long-term hypoxia. Of the diverse effects of HIF-1 alpha on cancer progression, hypoxia-induced cell migration was investigated. In transwell chambers, NDRG3 negatively regulated the migration and invasion of prostate cancer cells under hypoxia. An informatics analysis using Gene Expression Omnibus (GEO) revealed that NDRG3 downregulation is associated with prostate cancer metastasis and high expression of HIF-1 downstream genes. In cancer tissue arrays, NDRG3 expression was lower in prostate cancer tissues with a Gleason score of 8 or greater and was inversely correlated with HIF-1 alpha expression. Therefore, NDRG3 may have an anti-metastatic function in prostate cancer under a hypoxic microenvironment.