C2028T polymorphism in exon 12 and dinucleotide repeat polymorphism in intron 13 of the HIF-1α gene define HIF-1α protein expression in non-small cell lung cancer

SummaryObjectivesIn this study, we investigated whether polymorphisms of the HIF-1α gene may account for the patterns of HIF-1α protein expression in non-small cell lung carcinomas (NSCLC) and the expression of HIF-1α down-stream proteins.MethodsSpecific HIF-1α polymorphisms were assessed in a series of patients with NSCLC: (a) the C to T transition at nucleotide 1744 (position 2028 according to sequence with accession number NM_001530, which gives rise to Pro/Ser variation at codon 582), (b) the G to A nucleotide substitution at point 1790 (position 2046 according to sequence with accession number NM_001530, which gives rise to Ala/Thr variation at codon 588), and (c) the dinucleotide GT repeat polymorphism in intron 13. Immunohistochemistry for HIF-1α and down-stream proteins (VEGF, LDH-5, GLUT-1) was also performed in tumor material.ResultsA strong association of the P582S polymorphism and of GT repeat polymorphism higher than 14/14 with increased HIF-1α expression was noted. HIF-1α polymorphism did not relate to the expression of the HIF-1α downstream proteins analysed, but significant association of HIF-1α expression with LDH-5 was confirmed (p = 0.008).ConclusionsHIF-1α polymorphisms may have an important impact on HIF-protein stability and, eventually, function.