RESUMO
We analyzed a possible association between RUNX3 gene polymorphisms and haplotypes in Mexican patients with colorectal cancer (CRC). Genomic DNA samples were obtained from the peripheral blood of 176 Mexican patients with CRC at diagnosis and from 195 individuals that formed the control group. The polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism. Association was estimated by odds ratio (OR). The haplotypes and linkage disequilibrium were established using the Arlequin v3.5 software. We found that the RUNX3 polymorphisms analyzed were in Hardy-Weinberg equilibrium. The RUNX3 rs2236852 AA genotype and A allele showed association with CRC (OR = 0.39, 95%CI = 0.21-0.73, P < 0.01; OR = 0.65, 95%CI = 0.49-0.87, P < 0.01, respectively), while the rs6672420, rs11249206, and rs760805 polymorphisms did not show significant association with CRC. The TA haplotype (SNPs rs760805 and rs2236852) showed an increased risk for CRC (OR = 2.52, 95%CI = 1.47-4.30, P < 0.001). In conclusion, we found that the AA genotype and A allele of rs2236852 polymorphism confer a decreased CRC risk, while the TA haplotype appears to increase the risk of CRC development in Mexican patients.
Assuntos
Neoplasias Colorretais/genética , Subunidade alfa 3 de Fator de Ligação ao Core/genética , Predisposição Genética para Doença , Haplótipos , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Estudos de Casos e Controles , Feminino , Humanos , Masculino , México , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Adulto JovemRESUMO
The ZNF217 gene, a potential oncogene amplified and overexpressed in several cancers including colorectal cancer (CRC), acts as a transcription factor that activates or represses target genes. The polymorphisms rs16998248 (T>A) and rs35720349 (C>T) in coronary artery disease have been associated with reduced expression of ZNF217. In this study, we analyzed the 2 polymorphisms in Mexican patients with CRC. Genotyping of rs16998248 and rs35720349 sites was performed by polymerase chain reaction-restriction fragment length polymorphism in 203 Mexican Mestizos, 101 CRC patients, and 102 healthy blood donors. Although no statistical differences regarding genotype and allele frequencies of ZNF217 polymorphisms were observed (P > 0.05), linkage disequilibrium was significant in CRC patients (r(2) = 0.39, P < 0.0001), as a result of reduced AC haplotype frequency. Thus, the AC haplotype may protect against CRC.
Assuntos
Carcinogênese/genética , Neoplasias Colorretais/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Transativadores/genética , Estudos de Casos e Controles , Frequência do Gene/genética , Humanos , MéxicoRESUMO
We investigated whether the MDR1 C3435T polymorphism is associated with fibrocystic changes (FCC), infiltrating ductal breast cancer (IDBC), and/or clinical-pathological features of IDBC in Mexican patients. Samples from women who received surgical treatment in 2007 at the Centro Médico de Occidente (México) were included in the analysis. Genotyping was performed by polymerase chain reaction-restricted fragment length polymorphisms in 64 paraffin-embedded breast samples with IDBC, 64 samples with FCC, and 183 peripheral blood samples of healthy females designated as the healthy group (HG). The frequency of the T allele was 41, 45, and 52% for the FCC, IDBC, and HG samples, respectively. Significant differences were only found between the FCC and HG samples [odds ratio (OR) = 0.64, 95% confidence interval (CI) = 0.43-0.96; P = 0.032]. The prevalence of the T/T genotype was 8, 13, and 24% for FCC, IDBC, and HG samples, respectively. Again, statistical differences were only found between FCC and HG samples for the T/T genotype (OR = 0.28, 95%CI = 0.106-0.77; P = 0.009). Although the T allele and the T/T genotype were less frequent in the IDBC group than in the HG, the differences were not significant. Furthermore, no associations were found between the C3435T polymorphism and clinical-pathological features of the IDBC group. Both the FCC and IDBC groups had a high frequency of the C allele relative to the HG in this sample of women from Western Mexico.
Assuntos
Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Doença da Mama Fibrocística/genética , Polimorfismo de Nucleotídeo Único , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Estudos de Casos e Controles , Feminino , Doença da Mama Fibrocística/patologia , Expressão Gênica , Frequência do Gene , Genótipo , Humanos , México , Pessoa de Meia-Idade , Gradação de Tumores , Polimorfismo de Fragmento de RestriçãoRESUMO
Colorectal cancer (CRC) is characterized by enhanced expression and activity of several metalloproteinases (MMPs), including MMP13 and MMP7, which play an important role in tumor invasion and metastasis. The objective of this study was to analyze the association of functional MMP7-181A/G and MMP13-77A/G promoter polymorphisms with susceptibility to CRC in a Mexican population. Genomic DNA samples were obtained from peripheral blood of 102 CRC patients and 125 blood donors who were included as the control group. Identification of polymorphisms was based on polymerase chain reaction-restriction fragment length polymorphism methodology. The association was estimated by the odds ratio (OR) test. The results showed that MMP7-181A/G and MMP13-77A/G variants were associated with CRC. For MMP7-181A/G, the AA (P=0.02, OR=3.38, 95% confidence interval (CI)=1.16-9.84) and AG (P=0.01, OR=3.4, 95%CI=1.17-9.83) genotypes were associated with an increased risk of CRC. For MMP13-77A/G, the AA and AG genotypes were associated with CRC (AA genotype: P=0.04, OR=3.2, 95%CI=1.004-10.2; AG genotype: P=0.01, OR=4.08, 95%CI=1.3-13.07). In conclusion, AA and AG genotype carriers for both polymorphisms are at a higher risk of developing CRC in this Mexican population.
Assuntos
Neoplasias Colorretais/genética , Metaloproteinase 14 da Matriz/genética , Metaloproteinase 7 da Matriz/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/patologia , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , População , Regiões Promotoras GenéticasRESUMO
DNA repair proteins maintain DNA integrity; polymorphisms in genes coding for these proteins can increase susceptibility to colorectal cancer (CRC) development. We analyzed a possible association of MLH1 -93G>A and 655A>G and XRCC1 Arg194Trp and Arg399Gln polymorphisms with CRC in Mexican patients. Genomic DNA samples were obtained from peripheral blood of 108 individuals with CRC (study group) at diagnosis and 120 blood donors (control group) from Western Mexico; both groups were mestizos. The polymorphisms were detected by PCR-RFLP. Association was estimated by calculating the odds ratio (OR). We found that the MLH1 and XRCC1 polymorphisms were in Hardy- Weinberg equilibrium. The MLH1 655A>G polymorphism in the 655G allele was associated with a 2-fold increase risk for CRC (OR = 2.04 and 95% confidence interval (95%CI) = 1.12-3.69; P < 0.01), while the MLH1 -93G>A polymorphism allele was associated with a protective effect (OR = 0.60, 95%CI = 0.40-0.89; P = 0.01 in the -93A allele and OR = 0.32, 95%CI = 0.13-0.79; P = 0.01 in the AA genotype). The XRCC1 Arg194Trp and Arg399Gln polymorphisms did not show any significant associations. In conclusion, we found that MLH1 -93G>A and 655A>G polymorphisms are associated with CRC in Mexican patients.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Neoplasias Colorretais/genética , Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença , Proteínas Nucleares/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Frequência do Gene/genética , Humanos , México , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL , Proteína 1 Complementadora Cruzada de Reparo de Raio-X , Adulto JovemRESUMO
INTRODUCTION: Injuries to peripheral nerves can have different causes and may lead to disorders affecting mobility, sensitivity and loss of motor function as they progress. Weiss, in 1944, introduced tubulisation to promote the regeneration of a sectioned nerve. In this study the biomaterial Chitosan was used to induce and stimulate the regeneration of the sciatic nerve in dogs. At the same time, we took advantage of the characteristics offered by Chitosan to include the neurosteroid progesterone in its matrix, as a promoter of axonal growth. AIMS. The aim of our study was to determine the degree of regeneration of the sciatic nerve in dogs when axotomised tubulised with a Chitosan prosthesis steeped in the neurosteroid progesterone. MATERIALS AND METHODS: Young adult female dogs were used to evaluate the regeneration of the sciatic nerve induced at a standard of 15 mm; regeneration was determined by means of an axonal growth chamber. Nerve growth was studied through histological analysis and by electron microscope. RESULTS: The statistical analysis showed that there were no significant differences in the number of myelinated fibres between the experimental groups. The electron microscope images of the transmission in the regenerated nerves in the groups that were tubulised with Chitosan, with and without neurosteroid preloading, revealed an advanced regenerative process. This was evidenced by the fact that collagen fibres, elastin, Schwann cells and both myelinated and non myelinated fibres were observed in all cases. CONCLUSIONS: The regeneration of axotomised, tubulised nerves was achieved regardless of the treatment that was applied. The distal nerve segment that was analysed revealed a similar structure to that of a normal nerve.
Assuntos
Axotomia , Materiais Biocompatíveis/metabolismo , Quitina/análogos & derivados , Quitina/metabolismo , Regeneração Nervosa/fisiologia , Progesterona/metabolismo , Nervo Isquiático/fisiologia , Animais , Axônios/metabolismo , Axônios/ultraestrutura , Quitosana , Cães , Feminino , Humanos , Implantação de Prótese/métodos , Nervo Isquiático/ultraestruturaRESUMO
This study demonstrated that when the regeneration of the axotomized sciatic nerve is induced through tubulization with chitosan, this biomaterial does not induce immunostimulation or immunodepression in the dog. Canine females were distributed among three groups: an intact control group which was only isolated, an axotomized control group, and an axotomized group which was tubulized with 3% chitosan prostheses. In vitro culture and phagocytosis tests, as well as IgG and IgM serum concentrations, were determined in peripheral blood on days 0, 15, 30 and 60. The results showed that chitosan implants did not importantly affect the immune response.