title: 1513A>C polymorphism in the P2X7 receptor gene in patients with papillary thyroid cancer: correlation with histological variants and clinical parameters.
abstract: BACKGROUND
  The modulation of the purinergic receptor P2X7 may be implicated in human carcinogenesis. The 1513A>C and 489C>T polymorphisms of P2X7R gene induce loss of function and gain of function, respectively.
  
  
  OBJECTIVE
  The aim of the study was to assess the frequency of both 1513A>C and 489C>T polymorphisms in patients with papillary thyroid carcinoma (PTC) and to evaluate the possible association with clinical and histological features.
  
  
  METHODS
  P2X7R analysis was performed in lymphocytes from 121 PTC patients (100 women, 21 men; aged 43.4 +/- 13.6 yr), 100 matched healthy subjects, and 80 patients with nodular goiter.
  
  
  RESULTS
  The minor allele frequency for 1513A>C polymorphism in PTC patients with the classical variant was similar to controls (0.21 and 0.20, respectively), whereas it resulted in a significant increase in patients with the follicular variant (0.36; P = 0.01 vs. classical variant, and P = 0.005 vs. controls). In detail, 13.6% of patients with PTC follicular variant were homozygous for the 1513C allele, compared to 2.6% of patients with the classical variant and 2% of controls. Moreover, a positive relationship between 1513A>C polymorphism and either cancer diameter (Rho = 0.22; P = 0.02) or TNM stage (Rho = 0.38; P < 0.001) was found. No significant difference in the genotype frequency of 489C>T polymorphism between PTC patients and healthy controls was observed (0.42 and 0.47, respectively).
  
  
  CONCLUSIONS
  Our data show, for the first time, a strong association between 1513A>C polymorphism of P2X7R gene and the follicular variant of PTC. Further studies are needed to confirm the possible role of this polymorphism as a novel clinical marker of PTC follicular variant and its usefulness in selecting patients with different clinical outcome.
authors.affiliation: Department of Internal Medicine, University of Pisa, via Roma 67, 56126 Pisa, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Dardano
authors.forename: Simonetta
authors.initials: S
authors.lastname: Falzoni
authors.forename: Nadia
authors.initials: N
authors.lastname: Caraccio
authors.forename: Antonio
authors.initials: A
authors.lastname: Polini
authors.forename: Sara
authors.initials: S
authors.lastname: Tognini
authors.forename: Anna
authors.initials: A
authors.lastname: Solini
authors.forename: Piero
authors.initials: P
authors.lastname: Berti
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Virgilio
authors.forename: Fabio
authors.initials: F
authors.lastname: Monzani
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics / Q000502:physiology; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D018265:Carcinoma, Papillary, Follicular / Q000235:genetics; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006044:Goiter, Nodular / Q000235:genetics / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018048:Receptors, Purinergic P2 / Q000235:genetics*; D058486:Receptors, Purinergic P2X7; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D047368:Tumor Burden / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C546468:P2RX7 protein, human; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7