Polymorphisms of genes of TGF-beta pathway and susceptibility to colorectal cancer

Background: Genetic background implicated in cytokine network may have a key role in the susceptibility to colorectal cancer (CRC). The TGF-\u3b2 pathway is involved in several biological processes, including cell proliferation, differentiation, migration and apoptosis. Methods: rs1800471 SNP polymorphism of TGF- f1 rs334348 and rs334349 of TGF-\u3b2R1, rs900 of TGF-\u3b22 and rs4522809 of TGF-\u3b22R2 were typed in a group of 82 patients affected by sporadic CRC and in 237 age- and sex-matched healthy controls, using a competitive allele specific PCR assays (KASPar), developed by KBioscience (England). Results: No significant genetic contribution has been observed for 3 of the 5 SNPs tested. Indeed, a significant different allelic distribution between patients and controls has been observed for the polymorphism G\u2192C (rs1800471) responsible for an arginine vs. proline missense change (R25P) in codon 25 of the TGF-\u3b2 gene (P = 0.021). By this analysis, a weak protective role would emerge for the minor allele C in the susceptibility to the disease. Furthermore the analysis of genotype and allelic frequencies of rs4522809 showed a statistically significant difference (p =0,0016 and P = 0,0019 respectively) between patients and controls. Conclusions: All together these results, suggest that functional relevant SNPs of TGF-beta pathway might be involved in susceptibility to CRC, influencing the extension and severity of the disease