Hypoxia-inducible factor-1 polymorphisms associated with enhanced transactivation capacity, implying clinical significance

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Abstract
Hypoxia-inducible factor-1 (HIF-1) is a pivotal factor that regulates cellular responses to hypoxia and is presumably linked to regulation of angiogenesis and tumor growth. We assessed the difference in transcription activity of two HIF-1α polymorphic variants (P582S and A588T), along with molecular epidemiological study among head and neck squamous cell carcinoma (HNSCC) patients. Both HIF-1α variants revealed significantly higher transcription activity than wild-type (WT) did, under normoxic and hypoxic conditions ( P < 0.02). Furthermore, tumors from HNSCC patients with heterozygous alleles having P582S or A588T had significantly increased numbers of microvessels compared with those with homozygous WT ( P = 0.02). In addition, all patients with tumors of T1 (below 2 cm diameter) were WT, while 14 of 47 patients with tumors of ≥T2 were heterozygous. The elevated transactivation capacity of variant forms of HIF-1α implies a role of HIF-1α polymorphisms in generating individually different tumor progression.

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