Wilms' tumor susceptibility: possible involvement of FOXP3 and CXCL12 genes

Wilms' tumor is an embryonal neoplasm of the kidney that accounts for approximately 6 % of all childhood tumors. The chemokine CXCL12 (C-X-C chemokine ligand 12) and its ligand CXCR4 (C-X-C chemokine receptor type 4) are involved in the development of several organs, including the kidney, and are also associated with tumor growth and metastasis. FOXP3 (forkhead transcription factor 3) was initially described as a marker for regulatory T cells; however, its expression in several types of tumor cells has already been described and may have prognostic significance. The aim of the present study was to analyze rs3761548 and rs2232365 FOXP3 polymorphisms, as well as evaluate rs1801157 CXCL12 polymorphism in Wilms' tumor samples.

Polymorphisms were evaluated in 32 patients and 78 neoplasia-free controls. Genotypes of rs1801157 were determined using PCR-restriction fragment length polymorphism (PCR-RFLP) method, and genotypes of rs2232365 and rs3761548 were determined using allele-specific PCR (AS-PCR).

The case-control study indicated a significant association for allele A carriers of rs1801157 polymorphism in relation to Wilms' tumor susceptibility (OR = 5.261; 95 % CI 2.156 to 12.84; p = 0.0002). The opposite was observed in male carriers of G allele for rs2232365 polymorphism (OR 0.1164; 95 % CI 0.0227 to 0.5954; p = 0.0091) or when male and female subjects were analyzed (OR = 0.1304; 95 % CI 0.05013 to 0.3394; p < 0.0001).

All in all, these markers may contribute to this neoplasia susceptibility and progression; however, further studies are needed to real clarify their role in Wilms' tumor pathogenesis.