title: Strong association of CTLA-4 variation (CT60A/G) and CTLA-4 haplotypes with predisposition of Iranians to head and neck cancer.
abstract: BACKGROUND
  Variations in Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) affect the expression and function of this protein.
  
  
  OBJECTIVE
  We aimed to investigate the association of +49 A/G (rs231775), +1822 C/T (rs231779) and +6230 A/G (CT60, rs3087243) genetic variations, as well as the merged haplotypes in CTLA-4 gene with susceptibility to, or progression of head and neck cancer.
  
  
  METHODS
  Eighty patients with confirmed head and neck (HN) cancer (age 54.9 ± 16.1 years) and 85 healthy age/sex-matched controls (age 56.3 ± 12.4 years) were enrolled in the study. Genotypes were investigated by the PCR-RFLP method. Arlequin software package was used to check for Hardy-Weinberg equilibration, and to estimate the haplotypes.
  
  
  RESULTS
  At position +6230 A/G (CT60), AA genotype, as well as A allele was significantly decreased in patients with HN cancers than controls (18.8% vs. 40.7%, p=0.004; odds ratio=0.34, and 46.3% vs. 61.7, p=0.007; odds ratio=0.53%, respectively). Nearly the same results were obtained when we compared the subgroup of patients with squamous cell carcinoma of the HN (SCC-HN) with control subjects. The frequencies of genotypes and alleles at other positions were not significantly different between patients and controls, however ACG, GTA and GCA haplotypes emerged from three investigated loci occurred with significantly more frequencies in patients (p<0.0001), while ACA and GTG haplotypes were more frequent among controls (p<0.0001). Significant differences of haplotypes, genotypes and alleles frequencies resisted the Bonferroni correction.
  
  
  CONCLUSIONS
  Our results suggest that CT60 A allele, as well as ACA and GTG haplotypes in CTLA-4 gene may have protective roles against HN cancer in Iranian population, while ACG, GTA and specially GCA haplotypes may render susceptibility.
authors.affiliation: Shiraz Institute for Cancer Research, Head, Shiraz University of Medical Sciences, Shiraz, Iran, e-mail: ghaderia@sums.ac.ir.
authors.forename: Nasrollah
authors.initials: N
authors.lastname: Erfani
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Haghshenas
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Hoseini
authors.forename: Seyed Basir
authors.initials: SB
authors.lastname: Hashemi
authors.forename: Bijan
authors.initials: B
authors.lastname: Khademi
authors.forename: Abbas
authors.initials: A
authors.lastname: Ghaderi
mesh_terms: D000328:Adult; D000368:Aged; D060908:CTLA-4 Antigen / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D007492:Iran; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D060908:CTLA-4 Antigen