1513A>C Polymorphism in the P2X7 Receptor Gene in Patients with Papillary Thyroid Cancer: Correlation with Histological Variants and Clinical Parameters

Introduction: The modulation of the purinergic receptor P2X(7) may be implicated in human carcinogenesis. The 1513A>C and 489C>T polymorphisms of P2X(7)R 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: P2X(7)R 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 P2X(7)R 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. (J Clin Endocrinol Metab 94: 695-698, 2009)