Abstract
BackgroundHypoxia inducible factor 1α (HIF-1α) is a stress-responsive transcription factor to hypoxia and its expression is correlated to tumor progression and angiogenesis. Several single nucleotide polymorphisms (SNPs) of HIF-1α gene in the oxygen-dependent degradation (ODD) domain was reportedly associated with increased HIF-1α activity.ResultsIn this study, we focused on the relationship between SNP 1772 C > T (rs11549465) of HIF-1α gene and its breast cancer risk, as well as its correlation with HIF-1α expression and tumor angiogenesis. Ninety six breast cancer patients and 120 age-matched controls were enrolled. We found that 1772 T allele of HIF-1α gene was associated with increased breast cancer risk (adjusted OR = 14.51; 95% CI: 6.74-31.24). This SNP was not associated with clinicopathologic features of angiogenesis such as VEGF activity and the micro-vessel density and survival of breast cancer patients.ConclusionTaken together, the 1772 C > T of HIF-1α gene is a potential biomarker for breast cancer susceptibility.
Highlights
Hypoxia inducible factor 1α (HIF-1α) is a stress-responsive transcription factor to hypoxia and its expression is correlated to tumor progression and angiogenesis
The purpose of this study is to investigate the association between single nucleotide polymorphisms (SNPs) 1772 C > T of the HIF-1α gene in breast cancer patients and healthy control subjects
We found that T allele of the SNP 1772 C > T (P582S) of HIF-1α gene was significantly higher in 96 breast cancer patients than in 120 controls
Summary
Hypoxia inducible factor 1α (HIF-1α) is a stress-responsive transcription factor to hypoxia and its expression is correlated to tumor progression and angiogenesis. Several single nucleotide polymorphisms (SNPs) of HIF-1α gene in the oxygen-dependent degradation (ODD) domain was reportedly associated with increased HIF-1α activity. Single nucleotide polymorphisms (SNPs), the most common variants in human genome [1], are popular biomarkers for disease/cancer prediction and therapeutic evaluation [2,3,4,5,6,7,8]. Hypoxia inducible factor-1 (HIF-1) is a crucial transcription factor in cellular response to tumor hypoxia and is considered as an adverse prognostic factor in breast cancers [12,13,14]. The degradation of HIF-1α depends on prolyl hydroxylation. Oxygen-dependent prolyl hydroxylases [16,17] may hydroxylate the HIF-1α on proline
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