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Lack of relevance of HIF-1α polymorphisms in breast cancer in a Portuguese population.

We aimed to study the prevalence of Hypoxia inducible factor-1α (HIF-1α) P582S and A588T polymorphisms in a Portuguese breast cancer population and its effect on the transcriptional activity of HIF-1α in MCF7 breast adenocarcinoma cells. We performed a polymerase chain Reaction--restriction fragment length polymorphism (PCR-RFLP)-based genotyping of a Portuguese breast cancer population for two HIF-1α polymorphisms. Furthermore, by site-directed mutagenesis, we generated a variant form of HIF-1α and compared its transcriptional activity with the wild-type HIF-1α in MCF7 cells. There were no significant differences in genotypic frequencies for P582S and A588T between breast cancer patients and controls, nor between the transcriptional activity of the 582S mutant and the wild-type HIF-1α. In conclusion, there is no association between HIF-1α polymorphisms and incidence of breast cancer in the Portuguese examined population. Furthermore, the P582S mutation does not affect transcriptional activity of HIF-1α in breast cancer cells, contrary to previous findings in other cell lines, suggesting that the impact of this mutation is cell-type specific.