Single nucleotide polymorphisms in the hypoxia-inducible factor-1alpha (HIF-1alpha) gene in human sporadic breast cancer.

Background: DNA sequence variations in hypoxia-inducible factor-1alpha (HIF-1alpha) gene, which have been demonstrated to be correlated with tumor angiogenesis, may yield changes both in the production outcomes and in the activities of the gene. In this study, we investigated the relationship between three single nucleotide polymorphisms (SNPs) [C1772T and G1790A in exon 12 and C111A in exon 2 of the HIF-1alpha gene] in the HIF-1alpha gene coding regions and development of sporadic breast cancer in the Turkish population. These three polymorphisms result in an amino acid change from proline 582 to serine, from alanine 588 to threonine and from serine 28 to tyrosine, respectively.

Methods: Genomic DNA was isolated from 102 sporadic breast cancer patients and 102 healthy female controls. All three HIF-1alpha gene regions were amplified by PCR, and genotypes were determined by RFLP and DNA sequencing.

Results: There were no significant differences between patients and controls in terms of the distribution of C1772T and G1790A polymorphisms of HIF-1 gene (p >0.05). As for HIF-1alpha C111A polymorphism, we did not find CA and AA variants of the gene in either controls or patients. Multivariable logistic regression analysis was performed between CC and CT + TT genotypes of C1772T polymorphism. No significant differences were found between these two genotypes in terms of clinicopathological characteristics of the patients including age at enrollment, age at menarche and first delivery, number of full-term pregnancies, body mass index, use of oral contraceptives and postmenopausal hormones, family history of breast and ovarian cancers, menopausal status, histopathological features, oophorectomy, smoking habits, and alcohol consumption (p >0.05).

Conclusions: Our results suggest that none of the polymorphisms studied in the HIF-1alpha gene influence susceptibility to sporadic breast cancer. The present study is the first case-control study that investigates the association of HIF-1alpha polymorphisms with sporadic breast cancer in the Turkish population.