title: An investigation of relationships between hypoxia-inducible factor-1 alpha gene polymorphisms and ovarian, cervical and endometrial cancers.
abstract: BACKGROUND
  DNA sequence variations in HIF-1 alpha gene might yield changes both in the production outcomes and in the activities of the gene. Overexpression of the HIF-1 alpha subunit, resulting from intratumoral hypoxia and genetic alterations, has been demonstrated in common human cancers and is correlated with tumor angiogenesis and patient mortality. In this study, we aimed to determine how the three single nucleotide polymorphisms (SNPs, C1772T and G1790A exon 12, C111A exon 2) in the HIF-1 alpha gene coding regions affect the ovarian, cervical and endometrial cancer patients in the Turkish population. A study on this relationship has not been conducted to date.
  
  
  METHODS
  102 gynecologic cancer patients and 107 healthy controls were studied. Genotypes of the three polymorphisms were analyzed by PCR-RFLP.
  
  
  RESULTS
  There was no significant difference between ovarian cancer patients and controls in terms of the distribution of C1772T genotypes and alleles (P>0.05). However, there was a highly significant increase in the frequency of both CT 1772 and TT 1772 genotypes in patients with cervical and endometrial cancers compared with healthy controls. In fact, 1772T allele-carriers (CT+TT genotypes) showed an association with the risk of cervical and endometrial cancers compared to the wild type (OR=3.84, 95% CI: 1.65-8.93; OR=7.41, 95% CI: 2.33-23.59, respectively). C1772T polymorphism was not associated with family history concerning gynecologic and/or other cancer types, stages (I-IV) and grades of tumor, smoking habits and existence of other diseases that generate a hypoxic microenvironment even after multivariable logistic regression analysis. As for HIF-1 alpha G1790A genotypes, the frequencies of G alleles were 98% in ovarian patients and 100% in the control group. We found no significant difference in the genotype distribution and allele frequencies between the ovarian patients and healthy control subjects. There were no GA and AA genotypes among the cervical and endometrial cancer patients. As for HIF-1 alpha C111A polymorphism, we did not find CA and AA variants of the gene in controls or in any of the three types of patients.
  
  
  CONCLUSIONS
  Our results suggest that the C1772T polymorphism of the HIF-1 alpha may be associated with cervical and endometrial cancers.
authors.affiliation: Department of Medical Biology and Genetics, Faculty of Medicine, Gazi University, 06500 Besevler, Ankara, Turkey.
authors.forename: Ece
authors.initials: E
authors.lastname: Konac
authors.forename: H Ilke
authors.initials: HI
authors.lastname: Onen
authors.forename: Jale
authors.initials: J
authors.lastname: Metindir
authors.forename: Ebru
authors.initials: E
authors.lastname: Alp
authors.forename: Aydan Asyali
authors.initials: AA
authors.lastname: Biri
authors.forename: Abdullah
authors.initials: A
authors.lastname: Ekmekci
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit