Differential genetically determined expression of transforming growth factor-? (TGF-? pathway and of vascular endothelial growth factor-A (VEGF-A) might modulate the molecular "milieu" involved in the etio-pathogenesis of non-melanoma skin cancer (NMSC). We have evaluated the frequency of some functionally relevant SNPs of TGF-? and VEGF-A genes in 70 NMSC patients and 161 healthy controls, typed for TGF-?1 rs1800471, TGF-?2 rs900, TGF-?R1 rs334348 and rs334349, TGF-?R2 rs4522809 and VEGF-A rs3025039 SNPs. TGF-?R2 rs1800629G allele and related genotypes were found to be associated with a possible protective role against NMSC, whereas VEGF-A rs3025039T was associated with an increased risk. To evaluate the effect of genotype combinations on NMSC susceptibility, we determined the frequencies of 31 pseudo-haplotypes due to non-random linkage among alleles of loci not lying on the same chromosome. Two pseudo-haplotypes that imply a minor allele of TGF-?R2 or minor allele of VEGF-A SNPs combined with major alleles of the other SNPs were, respectively, associated with a protective effect, and susceptibility to NMSC. In addition, a pseudo-haplotype involving minor alleles of TGF-?2 rs900, TGF-?R1 rs334348 and rs4522809 SNPs might be a susceptibility marker for NMSC. In conclusion, our data suggest that a complex interplay among the genetic polymorphisms of TGF-?, TGF-? receptors and VEGF-A genes might influence the net effect of genetic background of the patients on NMSC development. This might be relevant in the risk evaluation, diagnosis and treatment of NMSC.
TGF-?/VEGF-A Genetic Variants Interplay in Genetic Susceptibility to Non-Melanocytic Skin Cance
Forte GI;
2022
Abstract
Differential genetically determined expression of transforming growth factor-? (TGF-? pathway and of vascular endothelial growth factor-A (VEGF-A) might modulate the molecular "milieu" involved in the etio-pathogenesis of non-melanoma skin cancer (NMSC). We have evaluated the frequency of some functionally relevant SNPs of TGF-? and VEGF-A genes in 70 NMSC patients and 161 healthy controls, typed for TGF-?1 rs1800471, TGF-?2 rs900, TGF-?R1 rs334348 and rs334349, TGF-?R2 rs4522809 and VEGF-A rs3025039 SNPs. TGF-?R2 rs1800629G allele and related genotypes were found to be associated with a possible protective role against NMSC, whereas VEGF-A rs3025039T was associated with an increased risk. To evaluate the effect of genotype combinations on NMSC susceptibility, we determined the frequencies of 31 pseudo-haplotypes due to non-random linkage among alleles of loci not lying on the same chromosome. Two pseudo-haplotypes that imply a minor allele of TGF-?R2 or minor allele of VEGF-A SNPs combined with major alleles of the other SNPs were, respectively, associated with a protective effect, and susceptibility to NMSC. In addition, a pseudo-haplotype involving minor alleles of TGF-?2 rs900, TGF-?R1 rs334348 and rs4522809 SNPs might be a susceptibility marker for NMSC. In conclusion, our data suggest that a complex interplay among the genetic polymorphisms of TGF-?, TGF-? receptors and VEGF-A genes might influence the net effect of genetic background of the patients on NMSC development. This might be relevant in the risk evaluation, diagnosis and treatment of NMSC.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
