Differential genetically determined expression of transforming growth factor-β (TGF-β 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-β and VEGF-A genes in 70 NMSC patients and 161 healthy controls, typed for TGF-β1 rs1800471, TGF-β2 rs900, TGF-βR1 rs334348 and rs334349, TGF-βR2 rs4522809 and VEGF-A rs3025039 SNPs. TGF-βR2 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-βR2 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-β2 rs900, TGF-βR1 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-β, TGF-β 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.

Letizia Scola, Maria Rita Bongiorno, Giusi Irma Forte, Anna Aiello, Giulia Accardi, Chiara Scrimali, et al. (2022). TGF-β/VEGF-A Genetic Variants Interplay in Genetic Susceptibility to Non-Melanocytic Skin Cancer. GENES, 13(7), 1-14 [10.3390/genes13071235].

TGF-β/VEGF-A Genetic Variants Interplay in Genetic Susceptibility to Non-Melanocytic Skin Cancer

Letizia Scola;Maria Rita Bongiorno;Giusi Irma Forte;Anna Aiello;Giulia Accardi;Chiara Scrimali;Rossella Spina;Domenico Lio
;
Giuseppina Candore
2022

Abstract

Differential genetically determined expression of transforming growth factor-β (TGF-β 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-β and VEGF-A genes in 70 NMSC patients and 161 healthy controls, typed for TGF-β1 rs1800471, TGF-β2 rs900, TGF-βR1 rs334348 and rs334349, TGF-βR2 rs4522809 and VEGF-A rs3025039 SNPs. TGF-βR2 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-βR2 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-β2 rs900, TGF-βR1 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-β, TGF-β 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.
Settore MED/05 - Patologia Clinica
Settore MED/04 - Patologia Generale
https://www.mdpi.com/2073-4425/13/7/1235
Letizia Scola, Maria Rita Bongiorno, Giusi Irma Forte, Anna Aiello, Giulia Accardi, Chiara Scrimali, et al. (2022). TGF-β/VEGF-A Genetic Variants Interplay in Genetic Susceptibility to Non-Melanocytic Skin Cancer. GENES, 13(7), 1-14 [10.3390/genes13071235].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/569202
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