1513A>C polymorphism in the P2X7 receptor gene in patients with papillary thyroid cancer: correlation with histological variants and clinical parameters

J Clin Endocrinol Metab. 2009 Feb;94(2):695-8. doi: 10.1210/jc.2008-1322. Epub 2008 Nov 18.

Abstract

Introduction: 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.

Aim: 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.

Patients and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / physiology
  • Carcinoma, Papillary / genetics*
  • Carcinoma, Papillary / pathology
  • Carcinoma, Papillary, Follicular / genetics
  • Case-Control Studies
  • DNA Mutational Analysis
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Goiter, Nodular / genetics
  • Goiter, Nodular / pathology
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Receptors, Purinergic P2 / genetics*
  • Receptors, Purinergic P2X7
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / pathology
  • Tumor Burden / genetics

Substances

  • Biomarkers, Tumor
  • P2RX7 protein, human
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2X7