RESUMO
We examined the correlations between the polymorphic alleles of the DNA repair genes XRCC1 (c.839G> A, rs25489; and c.1196A> G, rs25487), XPA (c.-4A> G, rs1800975), and XPD (c.2251A> C, rs13181) and the progression and severity of neoplasias in the bladder and kidney in patients of three distinct ethnic groups, Bashkir, Russians, and Tatar, residing in the Republic of Bashkorostan. The study enrolled 468 cancer patients and 351 healthy individuals. Genotyping for polymorphic alleles was carried out using the PCR-RFLP method. We identified a correlation between allele A of the c.839 G>A locus of the XRCC1 gene and the incidence of the bladder cancer (BC) and kidney cancer (KC) in the Tatar study group, using the additive genetic effects model (Odds Ratio (OR) = 5.23 and OR = 3.90). In turn, the heterozygous G/A genotype was present at a significantly higher frequency in the KC patients of Bashkir ethnic origin, compared with the control group (p = 0.0061, OR= 4.72). Additional analysis with consideration of participants' smoking status showed that the G/A genotype is significantly more frequent in smokers with BC (OR = 1.96, p = 0.05) then in healthy smokers. We also determined, using the recessive genetic model, that the genotype A/A of the c. 1196A>G locus of the XRCC1 gene was correlated with a higher risk of BC in the Russian cohort (OR = 2.29, p = 0.0082) and an increased incidence of KC in the Bashkir group (OR = 4.06, p = 0.05). A similar correlation was obtained for smokers. In contrast, the allele c.2251 A>C in the XPD gene correlated with a lower risk for BC and KC in the Tatars (p = 0.0003, OR = 0.48 and p < 0.0001, OR = 0.37) in the additive model and in the Bashkirs (p = 0.0083, OR = 0.12) and Russians (p = 0.0001, OR = 0.14) in the recessive model. Further, we uncovered that polymorphism c.839 G>A in the XRCC1 gene contributes to the progression of noninvasive and invasive BC and promotes KC at early and advanced stages of the disease. Thus, we identified similar correlations between DNA repair gene polymorphism and the incidence and progression of BC and KC. We propose that this result points to the involvement of common pathogenetic mechanisms in the initiation and progression of the urinary neoplasias.
Assuntos
Carcinoma de Células Renais/genética , Proteínas de Ligação a DNA/genética , Neoplasias da Bexiga Urinária/genética , Proteína Grupo D do Xeroderma Pigmentoso/genética , Idoso , Povo Asiático , Carcinoma de Células Renais/patologia , Progressão da Doença , Etnicidade/genética , Feminino , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Polimorfismo de Nucleotídeo Único , Neoplasias da Bexiga Urinária/patologia , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
We examined nine exons of transforming growth factor ß receptor type 1 (TGFßR1) gene in patients with chronic heart failure with different types of heart remodelling. We identified two missense mutations (c.457G>A (p.V1531) and c.1285A>C (p.Y229S)) and two synonym substitutions (c.1125A>C (p.Y377Y) and c.516A>G (p.S172S)), as well as polymorphisms at splicing site c.1024+24G>A (rs334354). Substitutions c.1285A>C (p.Y229S) and c.516A>G (p.S172S) were not previously described.