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-β pathway is involved in several biological processes, including cell proliferation, differentiation, migration and apoptosis. Methods: rs1800471 SNP polymorphism of TGF-ß1 rs334348 and rs334349 of TGF-βR1, rs900 of TGF-β2 and rs4522809 of TGF-β2R2 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→C (rs1800471) responsible for an arginine vs. proline missense change (R25P) in codon 25 of the TGF-β 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.