title: Association of FokI and PvuII polymorphisms with breast cancer staging and survival among Caucasian women: a prospective study.
abstract: OBJECTIVE
  Both vitamin D and estrogens play an important role in breast cell growth and differentiation. Therefore, we hypothesized that FokI polymorphism in the Vitamin D Receptor (VDR) gene, as well as PvuII polymorphism in the Estrogen Receptor (ESR) gene might be associated with progression of breast cancer. The aim of this study was to prospectively examine the association of these polymorphisms with histopathological features and prognosis among women with histologically proven breast cancer.
  
  
  METHODS
  Patient characteristics, tumor histopathology, and genotyping of one VDR polymorphism variant (FokI) and one ER polymorphism variant (PvuII) were recorded. Patients were also routinely followed up.
  
  
  RESULTS
  There was a significant difference regarding nodal stage (p<0.001) between the different genotypes of FokI polymorphisms (FF, Ff, ff), even though a trend was also detected in the frequency between ductal and lobular type, as well as tumor size (p=0.077). When further analysis was performed regarding patients whose polymorphism included the f allele, we found statistically significant differences in tumor size (p<0.001), nodal stage (p=0.03), tumor grade (p=0.04) and lymphovascular invasion (p<0.001), while no differences in nodal status, distant metastases and tumor stage were noticed. No significant associations were found between any of the PvuII polymorphism variants and tumor histopathology and stage. No statistical significance was proven between FokI polymorphism's variants or f allele and overall or progression-free survival. Statistically significant associations between overall and progression- free survival and PvuII polymorphism's variants was demonstrated (p<0.001).
  
  
  CONCLUSIONS
  The f allele was associated with the presence of lymphovascular invasion and poorly differentiated tumors, whereas the PP genotype was associated with increased overall and progression-free survival, suggesting that this variant is related to a more favorable prognosis.
authors.affiliation: 2nd Department of Surgery, Aretaieion Hospital, University of Athens, Athens, Greece.
authors.forename: Anneza I
authors.initials: AI
authors.lastname: Yiallourou
authors.forename: Emmanouel
authors.initials: E
authors.lastname: Ekonomou
authors.forename: Vassilios
authors.initials: V
authors.lastname: Tsamadias
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Nastos
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Karapanos
authors.forename: Ioannis
authors.initials: I
authors.lastname: Papaconstantinou
authors.forename: Theodosios
authors.initials: T
authors.lastname: Theodosopoulos
authors.forename: John
authors.initials: J
authors.lastname: Contis
authors.forename: Efstathios
authors.initials: E
authors.lastname: Papalambros
authors.forename: Dionysios
authors.initials: D
authors.lastname: Voros
authors.forename: John
authors.initials: J
authors.lastname: Psychogios
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D015257:DNA-Cytosine Methylases; D015252:Deoxyribonucleases, Type II Site-Specific; D005260:Female; D006801:Humans; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D018167:Receptors, Calcitriol / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D018167:Receptors, Calcitriol; C047084:DNA modification methylase PvuII; D015257:DNA-Cytosine Methylases; C035042:endodeoxyribonuclease FokI; D015252:Deoxyribonucleases, Type II Site-Specific