A loss-of-function polymorphic mutation in the P2X7 receptor gene in patients with papillary thyroid cancer

Extracellular nucleotides, via specific plasma membrane receptors (P2Rs) of the X and Y subtype, modulate several cell functions, including cell-to-cell cross talk. We have previously demonstrated the expression of several functional P2XRs subtypes, including P2X7, in primary human thyrocytes. P2X7 is the main player in inflammation and immunomodulation; a strong expression of this receptor has been shown in several human solid tumors. Polymorphisms of the gene encoding for P2X7 have been described; among these, 1513AOC induces loss-of-function while 489 COT gain-of-function of the receptor. We evaluated the presence of 1513AOC and 489COT polymorphisms in patients with papillary thyroid carcinoma (PTC). P2X7R genotypic analysis was performed in 83 patients with PTC (70 women; mean age 43G13 yrs; 29 with diameter !1 cm; 33 with follicular and 50 with classical variant) and 100 healthy subjects (Bone Marrow Bank donors, Ferrara). The single nucleotide polymorphisms were analyzed in genomic DNA samples by the TaqMan MGB probe technique. Results are summarized in the table. Increased homozygous substitution 1513AOC was detected only in patients with the follicular variant (22%). A significant correlation with PTC dimension was also observed (PZ0.02). No differences were detected in the allelic frequencies for 489COT. Overall, our data demonstrate an increased prevalence of 1513AOC polymorphism in patients with PTC. This loss-of-function polymorphism characterized the follicular variant and correlated with cancer dimension. Further studies are needed to evaluate the role of 1513AOC polymorphism as a novel clinical marker of differentiated thyroid carcinoma.