A polymorphism in FAS gene promoter associated with increased risk of nasopharyngeal carcinoma and correlated with anti-nuclear autoantibodies induction

Besma Bel Hadj Jrad, Wijden Mahfouth, Noureddine Bouaouina, Sallouha Gabbouj, Slim Ben Ahmed, Mondher Ltaïef, Majida Jalbout, Lotfi Chouchane

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Loss of FAS (CD95) expression is a common feature of malignant transformation, which has been related to loss of epithelial cell differentiation and loss of sensitivity to apoptosis. We investigated the potential association between FAS promoter polymorphism and the genetic susceptibility to the Epstein-Barr virus (EBV)-related nasopharyngeal carcinoma. The in vivo functional significance of the FAS polymorphism was investigated by assessing the correlation between FAS genotypes and the presence of autoantibodies to cytoskeleton and nuclear antigens frequently detected in nasopharyngeal carcinoma. We determined the FAS polymorphism distributions by RFLP-PCR in 170 patients with nasopharyngeal carcinoma and in 224 sex and age-matched controls. We used ELISA and the immunofluorescence analysis to characterize the presence of IgG autoantibodies to the cytoskeleton and nuclear proteins in patients' sera. A significantly increased risk of nasopharyngeal carcinoma was associated with heterozygote FAS-A/G (OR=2.00, P=0.001) and homozygote FAS-G/G (OR=3.19, P=0.0001) variants. The increased frequency of FAS-G/G genotype is correlated with the presence of anti-nuclear autoantibodies in patients with nasopharyngeal carcinoma (P=0.0298). Our results demonstrated that FAS promoter polymorphism was significantly associated with the nasopharyngeal carcinoma in Tunisians. The anti-nuclear autoantibodies induction was also found to be related to FAS polymorphism. The FAS promoter polymorphism associated not only with the increased risk of nasopharyngeal carcinoma in Tunisians but also with immune response deregulation observed in this cancer.

Original languageEnglish
Pages (from-to)21-27
Number of pages7
JournalCancer Letters
Volume233
Issue number1
DOIs
Publication statusPublished - 20 Feb 2006
Externally publishedYes

Fingerprint

Autoantibodies
Genes
Cytoskeleton
Genotype
Nuclear Antigens
Homozygote
Genetic Predisposition to Disease
Heterozygote
Nuclear Proteins
Nasopharyngeal carcinoma
Human Herpesvirus 4
Restriction Fragment Length Polymorphisms
Fluorescent Antibody Technique
Cell Differentiation
Immunoglobulin G
Epithelial Cells
Enzyme-Linked Immunosorbent Assay
Apoptosis
Polymerase Chain Reaction
Serum

Keywords

  • Apoptosis
  • Autoantibodies
  • FAS
  • Nasopharyngeal carcinoma
  • Polymorphism

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

A polymorphism in FAS gene promoter associated with increased risk of nasopharyngeal carcinoma and correlated with anti-nuclear autoantibodies induction. / Bel Hadj Jrad, Besma; Mahfouth, Wijden; Bouaouina, Noureddine; Gabbouj, Sallouha; Ahmed, Slim Ben; Ltaïef, Mondher; Jalbout, Majida; Chouchane, Lotfi.

In: Cancer Letters, Vol. 233, No. 1, 20.02.2006, p. 21-27.

Research output: Contribution to journalArticle

Bel Hadj Jrad, Besma ; Mahfouth, Wijden ; Bouaouina, Noureddine ; Gabbouj, Sallouha ; Ahmed, Slim Ben ; Ltaïef, Mondher ; Jalbout, Majida ; Chouchane, Lotfi. / A polymorphism in FAS gene promoter associated with increased risk of nasopharyngeal carcinoma and correlated with anti-nuclear autoantibodies induction. In: Cancer Letters. 2006 ; Vol. 233, No. 1. pp. 21-27.
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AU - Gabbouj, Sallouha

AU - Ahmed, Slim Ben

AU - Ltaïef, Mondher

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AB - Loss of FAS (CD95) expression is a common feature of malignant transformation, which has been related to loss of epithelial cell differentiation and loss of sensitivity to apoptosis. We investigated the potential association between FAS promoter polymorphism and the genetic susceptibility to the Epstein-Barr virus (EBV)-related nasopharyngeal carcinoma. The in vivo functional significance of the FAS polymorphism was investigated by assessing the correlation between FAS genotypes and the presence of autoantibodies to cytoskeleton and nuclear antigens frequently detected in nasopharyngeal carcinoma. We determined the FAS polymorphism distributions by RFLP-PCR in 170 patients with nasopharyngeal carcinoma and in 224 sex and age-matched controls. We used ELISA and the immunofluorescence analysis to characterize the presence of IgG autoantibodies to the cytoskeleton and nuclear proteins in patients' sera. A significantly increased risk of nasopharyngeal carcinoma was associated with heterozygote FAS-A/G (OR=2.00, P=0.001) and homozygote FAS-G/G (OR=3.19, P=0.0001) variants. The increased frequency of FAS-G/G genotype is correlated with the presence of anti-nuclear autoantibodies in patients with nasopharyngeal carcinoma (P=0.0298). Our results demonstrated that FAS promoter polymorphism was significantly associated with the nasopharyngeal carcinoma in Tunisians. The anti-nuclear autoantibodies induction was also found to be related to FAS polymorphism. The FAS promoter polymorphism associated not only with the increased risk of nasopharyngeal carcinoma in Tunisians but also with immune response deregulation observed in this cancer.

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