Implicações do polimorfismo genético de cyp1a1, gstm1 e gstt1 na suscetibilidade do carcinoma espinocelular da laringe

• Autor(a) principal: Silva Junior, Raimundo Lima da
• Data de Publicação: 2008
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UFG
• dARK ID: ark:/38995/0013000001q1h
• Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/6205
• topic: CEC da laringe; Suscetibilidade; CYP1A1m1; GSTM1; GSTT1; Farmacogenética; CEC of larinx; Suscetibility; Pharmacogenetics; BIOQUIMICA::BIOLOGIA MOLECULAR

The larynx is a tubular organ of the aerodigestive tract whose main function is the production of voice, in addition to tasks related to the protection of the lower airways and swallowing food. The squamous cell carcinoma presents itself as a multifactorial disease and epigenetic being influenced by environmental factors, behavioural and relate to the individual. Several polymorphic genes that encode enzymes involved in the biotransformation of the carcinogens have been associated to the development of cancer, especially in squamous cell carcinoma of head and neck. The CYP1A1m, GSTM1 and GSTT1 genes which catalyzes the oxidation of PAHs in phenolic and epoxides products. The purpose of this study was to evaluate the epidemiological data of patients diagnosed with squamous cell carcinoma of the larynx from the Cancer Registry of Population basis of Goiânia and from Association of Cancer Combat in Goiânia, analyzing data from 63 medical records followed in a period of 6 year; establish the allelic profiles of the gene CYP1A1m, GSTM1 and GSTT1 in casecontrol groups investigating the degrees of suscetibility of patients diagnosed with squamous cell carcinoma (SCC) of the larynx, according to smoking and alcoholism habits. In total 112 samples were evaluated, 63 from patients with SCC of the larynx and 49 patients in the control group. The CEC of the larynx was about 3,5 times more frequent in men than in women. The rate of survival on general was approximately 66% to 6 years. The smoking and ethilic habits associated have a significantly lower survival. No significant differences were found in the staging analysis and treatment of patients. Were found allelic frequencies of CYP1A1m1 of 52,4% (34/62) and 63,3% (31/49) for the wild allele T and 44,4% (28/62) and 34,7% (18/49) for the mutant allele C. There were no statistically significant associations between allelic variants and genotypic CYP1A1m1 with squamous cell carcinoma of the larynx. Positive genotypic frequencies were observed for the genes GSTM1 and GSTT1 of 41.3% (26/63) and 54.0% (34/63) to the patients with laryngeal cancer, and 49,0% (24/49) and 51,0% (25/49) for the control group, respectively. For the assessment of genotype GSTM1 (null) and GSTT1 (null), the patients if the case group had 58,7% (37/63) and 46,0% (29/63) of genotypes for GSTM1 null and GSTT1, while the patients in the control group showed 51,0% (25/49) and 40,8% (20/49). There was no statistically significance in associations of genotypic variants GSTM1 (null) and GSTT1 (null) with the larynx squamous cell carcinoma. In this context, an experimental study was accomplished in the intention of evaluating the function of the genes Cyp and Gst in the metabolism of the Cyclophosphamide. This study addressed the Cyclophosphamide toxicological evaluation and analysis of the polymorphism of Cyp2a29 and Gstp1 BALB/c genes in mice, correlating them with the toxicity of drugs through the assessment of organs commonly affected. It was determinated the DL50 of the 474mg/kg. Subsequently, another 40 mice were used on the assessment of the genetic polymorphism of genes Cyp2a29 and Gstp1. As for toxicity, cyclophosphamide caused reduction in body weight at different doses and kidneys, spleen, liver, heart and lungs. The animals that received a dose of 500mg/Kg died in 24 hours, three animals with a dose of 250mg/Kg died the end of one week. The evaluation of toxicity showed changes of varying degrees of congestion observed in the spleen, liver and heart. There were not found statistically significant differences between the frequencies of allelic and genotypic to Cyp2a29 and Gstp1 in groups of animals studied. This observation should be probably the characteristic line BALB/c are isogenic. Studies that make the use se of tests of genetic suscetibility, epidemic evaluation, combined to the evaluation anatomopathological they allow the study of the interaction genetic atmosphere and a possible standardization of various chemotherapy protocols for treatment.