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

• Published in: The journal of clinical endocrinology and metabolism Vol. 94; no. 2; pp. 695 - 698
• Main Authors: Dardano, Angela, Falzoni, Simonetta, Caraccio, Nadia, Polini, Antonio, Tognini, Sara, Solini, Anna, Berti, Piero, Virgilio, Francesco Di, Monzani, Fabio
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Oxford University Press 01.02.2009; Endocrine Society
• Subjects: Adult; Alleles; Biological and medical sciences; Biomarkers, Tumor - genetics; Biomarkers, Tumor - physiology; Carcinogenesis; Carcinoma, Papillary - genetics; Carcinoma, Papillary - pathology; Carcinoma, Papillary, Follicular - genetics; Case-Control Studies; DNA Mutational Analysis; Endocrinopathies; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Gene Frequency; Gene polymorphism; Genetic Predisposition to Disease; Goiter; Goiter, Nodular - genetics; Goiter, Nodular - pathology; Humans; Lymphocytes; Male; Malignant tumors; Medical sciences; Middle Aged; Papillary thyroid cancer; Papillary thyroid carcinoma; Polymorphism; Polymorphism, Single Nucleotide; Receptors, Purinergic P2 - genetics; Receptors, Purinergic P2X7; Thyroid cancer; Thyroid Neoplasms - genetics; Thyroid Neoplasms - pathology; Thyroid. Thyroid axis (diseases); Tumor Burden - genetics; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Endocrinopathy; Human; Obesity; Correlation; Papillary carcinoma; Genetic variability; Nutrition; Thyroid diseases; Nutrition disorder; Genotype; Patient; Metabolic diseases; Histology; Malignant tumor; P2X7 purinergic receptor; Variant; Thyroid cancer; Gene; Genetics; Endocrinology; Nutritional status; Cancer; Polymorphism
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2008-1322

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.