title: E-cadherin genetic variants predict survival outcome in breast cancer patients.
abstract: E-cadherin is a major component of adherens junctions that regulates cell shape and maintains tissue integrity. A complete loss or any decrease in cell surface expression of E-cadherin will interfere with the cell-to-cell junctions' strength and leads to cell detachment and escape from the primary tumor site. In this prospective study, three functional single nucleotide polymorphisms (-347G/GA, rs5030625; -160C/A, rs16260; +54C/T, rs1801026), were found to modulate E-cadherin expression.
  
  
  
  577 DNA samples from breast cancer (BC) cases were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
  
  
  
  We detected no significant correlations between each polymorphism and the clinical parameters of the patients whereas the GACC haplotype was significantly associated with low SBR grading. Overall survival analysis showed that both -347G/G and +54C/C wild (wt) genotypes had a significantly worse effect compared to the other genotypes (non-wt). Moreover, carrying simultaneously both the -347 and +54 wt genotypes confers a significantly higher risk of death. However, with metastatic recurrence, the death-rate was null in patients carrying the non-wt genotypes, and attained 37% in those carrying the wt genotype. A multivariate analysis showed that these two polymorphisms are independent prognostic factors for overall survival in BC patients.
  
  
  
  Our results support the fact that E-cadherin genetic variants control disease severity and progression and could be a marker of disease outcome. These findings could be useful in selecting patients that should be monitored differently.
authors.affiliation: Laboratory of Molecular Immuno-Oncology, Faculty of Medicine of Monastir, Monastir University, 5019, Monastir, Tunisia.|Faculty of Sciences of Bizerte, Carthage University, Bizerte, Tunisia.
authors.forename: Hager
authors.initials: H
authors.lastname: Memni
authors.affiliation: Laboratory of Molecular Immuno-Oncology, Faculty of Medicine of Monastir, Monastir University, 5019, Monastir, Tunisia.|Higher Institute of Biotechnology of Monastir, Monastir University, Monastir, Tunisia.
authors.forename: Yosra
authors.initials: Y
authors.lastname: Macherki
authors.affiliation: Laboratory of Molecular Immuno-Oncology, Faculty of Medicine of Monastir, Monastir University, 5019, Monastir, Tunisia.|Higher Institute of Biotechnology of Monastir, Monastir University, Monastir, Tunisia.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Klayech
authors.affiliation: Laboratory of Molecular Immuno-Oncology, Faculty of Medicine of Monastir, Monastir University, 5019, Monastir, Tunisia.|Faculty of Sciences of Bizerte, Carthage University, Bizerte, Tunisia.
authors.forename: Ahlem
authors.initials: A
authors.lastname: Ben-Haj-Ayed
authors.affiliation: Cancer Research Chair, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Karim
authors.initials: K
authors.lastname: Farhat
authors.affiliation: Laboratory of Molecular Immuno-Oncology, Faculty of Medicine of Monastir, Monastir University, 5019, Monastir, Tunisia.
authors.forename: Yassmine
authors.initials: Y
authors.lastname: Remadi
authors.affiliation: Laboratory of Molecular Immuno-Oncology, Faculty of Medicine of Monastir, Monastir University, 5019, Monastir, Tunisia.
authors.forename: Sallouha
authors.initials: S
authors.lastname: Gabbouj
authors.affiliation: Laboratory of Molecular Immuno-Oncology, Faculty of Medicine of Monastir, Monastir University, 5019, Monastir, Tunisia.
authors.forename: Wijden
authors.initials: W
authors.lastname: Mahfoudh
authors.affiliation: Laboratory of Molecular Immuno-Oncology, Faculty of Medicine of Monastir, Monastir University, 5019, Monastir, Tunisia.|Department of Cancerology and Radiotherapy, Farhat Hached University Hospital, Sousse University, Sousse, Tunisia.
authors.forename: Nadia
authors.initials: N
authors.lastname: Bouzid
authors.affiliation: Laboratory of Molecular Immuno-Oncology, Faculty of Medicine of Monastir, Monastir University, 5019, Monastir, Tunisia.|Department of Cancerology and Radiotherapy, Farhat Hached University Hospital, Sousse University, Sousse, Tunisia.
authors.forename: Noureddine
authors.initials: N
authors.lastname: Bouaouina
authors.affiliation: Laboratory of Genetic Medicine and Immunology, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, Qatar.
authors.forename: Lotfi
authors.initials: L
authors.lastname: Chouchane
authors.affiliation: Laboratory of Molecular Immuno-Oncology, Faculty of Medicine of Monastir, Monastir University, 5019, Monastir, Tunisia.|Department of Anatomy and Pathologic Cytology, Fattouma Bourguiba University Hospital, Monastir University, Monastir, Tunisia.
authors.forename: Abdelfattah
authors.initials: A
authors.lastname: Zakhama
authors.affiliation: Laboratory of Molecular Immuno-Oncology, Faculty of Medicine of Monastir, Monastir University, 5019, Monastir, Tunisia. elham.hassen@isbm.rnu.tn.|Higher Institute of Biotechnology of Monastir, Monastir University, Monastir, Tunisia. elham.hassen@isbm.rnu.tn.
authors.forename: Elham
authors.initials: E
authors.lastname: Hassen
mesh_terms: D000328:Adult; D015703:Antigens, CD; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D015820:Cadherins / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D014644:Genetic Variation; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D016019:Survival Analysis
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins
keywords: Breast cancer; E-cadherin; Prognosis; SNP