RESUMO
Activating mutation in K-ras gene is a key event in the pathogenesis of colon carcinoma. This study analyses frequency of this mutation in different age groups of colorectal cancer patients residing in North-Western Russia, and examines its relationship with essential clinical characteristics of tumor disease.
Assuntos
Envelhecimento/genética , Neoplasias do Colo/genética , Genes ras/genética , Mutação , Neoplasias Retais/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/patologia , Neoplasias do Colo/epidemiologia , Neoplasias do Colo/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Mutação , Reação em Cadeia da Polimerase , Neoplasias Retais/epidemiologia , Neoplasias Retais/patologia , Federação RussaRESUMO
The genetic polymorphism of metabolizers of tobacco smoke carcinogens can influence individual susceptibility to lung cancer. The study was concerned with the Mspl-polymorphism of the CYP1A1 gene responsible for encoding aryl hydrocarbon hydroxylase. It also plays a role in the activation of polycyclic aromatic hydrocarbons (PAH). The CYP1A1 alleles and genotype distribution in 146 lung cancer patients was compared with that in 230 healthy donors. Another control group consisted of 259 "cancer-resistant" subjects, i.e. tumor-free smokers and non-smokers aged 75 and more. The CYP1A1 allele incidence (19%) in patients with squamous lung cancer was significantly higher than in the control cohorts (11%) which is consistent with the leading role of PAH in the etiology of this pathology.
Assuntos
Hidrocarboneto de Aril Hidroxilases/genética , Citocromo P-450 CYP1A1/genética , Frequência do Gene , Neoplasias Pulmonares/genética , Proteínas de Membrana/genética , Polimorfismo Genético , Serina Endopeptidases/genética , Doadores de Tecidos , Adulto , Idoso , Hidrocarboneto de Aril Hidroxilases/metabolismo , Estudos de Casos e Controles , Ativação Enzimática/genética , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Neoplasias Pulmonares/enzimologia , Masculino , Pessoa de Meia-Idade , Fumar/efeitos adversosRESUMO
L-MYC and GSTMI polymorphisms were studied in glioma patients. L-MYC allele frequency in patients (L: 61/114 (54%); S: 53/114 (46%)) and controls (L: 108/204 (53%); S: 96/204 (47%)) was identical. S allele was associated with certain unfavourable clinical features of the disease. In particular, its frequency was 26/42 (62%) in relapse vs. 26/68 (38%) in relapse-free disease (p < 0.05). GSTMI "null" genotype was identified in both patients and healthy donors (48%). GSTMI-deficient genotypes were significantly predominant in patients with grade III-IV gliomas as compared with grade I-II tumors (p < 0.05). Patients, but not donors, frequently revealed a combination of SS L-MYC homozygosity and GSTMI (-) variant (p < 0.01) as well as an association of LL L0-MYC homozygosity and GSTMI (+) genotype (p < 0.05).
Assuntos
Neoplasias Encefálicas/genética , Genes myc/genética , Glioma/genética , Glutationa Transferase/genética , Polimorfismo Genético , Alelos , Neoplasias Encefálicas/enzimologia , Estudos de Casos e Controles , Intervalo Livre de Doença , Genótipo , Glioma/enzimologia , Homozigoto , HumanosRESUMO
By the restriction analysis method we established that methylation of the 5'-end cytosine in 5'-m5CC-3' duplexes had individual specific features. This genetic peculiarity did not change even in DNA from human stomach carcinomas.
Assuntos
Citosina/análogos & derivados , DNA/genética , Variação Genética , Citosina/metabolismo , DNA/metabolismo , Sondas de DNA , Genes ras , Humanos , Neoplasias Gástricas/genética , Úlcera Gástrica/genéticaRESUMO
A method of the restriction analysis by Msp I enzyme has been used to analyze the 12th codon of Ha-ras-1 protooncogene in 10 human carcinomas and in the stomach mucosa adjacent to them their 5 metastases into the regional lymph nodes and in 2 ulcers. No point mutation was found.
Assuntos
Adenocarcinoma/genética , Códon/genética , Genes ras/genética , Proto-Oncogenes/genética , RNA Mensageiro/genética , Úlcera Gástrica/genética , DNA/genética , DNA de Neoplasias/genética , Humanos , Metástase Linfática , Biologia Molecular , Mutação , Proto-Oncogene MasRESUMO
Ha-ras restriction fragments' length polymorphism (RFLP) in white blood cells and stomach tissues from patients with carcinoma and ulcer of the stomach was examined. Genomic DNAs were digested with Xho I, Pvu II, Pst I, Msp I, Bcn I, Mva I, Bsp RI. No Ha-ras-1 polymorphic variants specifically associated with the cancer disease were detected. RFLP of the 3'-noncoding sequence of c-Ha-ras-1 gene had got features of the definite human population. The cells forming the tissue were examined and individual peculiarity of the methylated residues disposition seemed to influence RFLP of the 5'-noncoding sequence of c-Ha-ras-1.
