Hypoxia-inducible factor-1α polymorphisms are associated with genetic aberrations in lung cancer.

摘要: Background and objective:  The transcription factor, hypoxia-inducible factor-1 (HIF-1), is a master regulator of hypoxia, including repression DNA repair systems, resulting in genomic instability cancer cells. roles the polymorphic HIF-1α variants, C1772T (P582S) G1790A (A588T), which are known to enhance transcriptional activity, were evaluated lung cancers. Methods:  polymorphisms assessed by direct sequencing total 83 patients (42 adenocarcinomas, 30 squamous cell, four adenosquamous cell seven small carcinomas) 110 healthy control subjects. relationship between these frequently observed genetic and/or epigenetic aberrations, TP53 loss heterozygosity (LOH), 1p34 LOH, retinoblastoma-1 (RB1) p16 inactivation epidermal growth factor receptor was then assessed. Results:  There no significant differences genotype frequencies for either or controls. However, frequency HIF1A variant allele significantly higher with LOH (P = 0.015). Among adenocarcinoma patients, individuals alleles polymorphism showed (P = 0.047), (P = 0.009), (P = 0.008) tumours. vitro activity variants A549 cells greater than that wild type under normoxic hypoxic conditions, especially P582S containing mutant p53 (P < 0.0005 P < 0.005, respectively). Conclusions:  These findings indicate functional gene may have an important impact on carcinogenesis, possibly increasing instability.