The results from the published studies on the association between hypoxia-inducible factor-1(Hif-1/HIF-1) polymorphisms and cancer risk are conflicting.
The results showed that HIF-1aC1772T 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).
A subset of relevant clinically observed mutations to pVHL are thought to cause weaker binding of HIF-1α and are associated with cancer and cardiovascular diseases.
Our meta-analysis suggests that the substitution of C allele with T at HIF-1α gene C1772T polymorphism is a risk factor of cancer, especially for cervical, head and neck cancer, pancreatic cancer and renal cell carcinoma.
Expression of C1772THIF-1α in HIF-1α knockout cancer cells showed higher expression levels and stabilization of HIF-1α mRNA compared with the wild-type.
The aim of this study was to analyze the possible influence of HIF-1α genetic polymorphisms on cancer susceptibility, tumor aggressiveness, and survival of patients with early-stage cervical cancer.
Subgroup analysis by ethnicity suggested that HIF1APro582Ser polymorphism might increase an individual's susceptibility to digestive tract cancer in Asian populations.
This meta-analysis demonstrates that the HIF-1α -1790G>A polymorphism is associated with a significantly increased risk of digestive tract cancer, while the -1772C>T polymorphism is not.
However, the prognostic value of single nucleotide polymorphisms (SNPs) in the HIF1A gene remains to be determined in most cancer types, including colorectal cancer (CRC).
A statistically significant association between the HIF-1α 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).
Our findings suggest that the HIF-1αA588T polymorphism is significantly associated with higher cancer risk and the P582S polymorphism is significantly associated with pancreatic cancer risk.
The results demonstrated that there were significant association between the HIF-1αC1772T polymorphism and cancer susceptibility under four genetic models (TT vs. CC: OR = 1.63, 95% CI = 1.02-2.60; CT + TT vs. CC: OR = 1.15, 95% CI = 1.01-1.34; TT vs. CT + CC: OR = 2.11, 95% CI = 1.32-3.77; T vs. C: OR = 1.21, 95% CI = 1.04-1.41).
Further subgroup analyses indicated that the C variant of HIF-1αC1772T polymorphism may increase the risk of GIT cancer among Asian populations, but not among Caucasian populations.
K477RHIF-1α mutation and specific cancer-associated Parkin mutations largely abolish the functions of Parkin to ubiquitinate HIF-1α and inhibit cancer metastasis.
In conclusion, this study indicated that HIF-1αC1772T polymorphism was significantly associated with increased risk of malignancy development for Asians.
Hypoxia-inducible factor 1a (HIF-1a), a key regulator of cancer metabolism, migration and angiogenesis that is stably expressed in RCCs by virtue of a genetic mutation in the von Hippel-Lindau (VHL) tumor-suppressor protein, was impeded by auraptene, which blocked HIF-1a translation initiation without causing cytotoxicity.